The human brain contains billions of neurons working together to process the vast array of information we receive from our environment. These neurons communicate at junctions known as synapses, where chemical packages called vesicles released from one neuron stimulate a response in another. This synaptic communication is crucial for our ability to think, learn and remember.

However, this activity depends on a complex interplay of proteins, whose balance and location within the neuron are tightly controlled. Any disruption to this delicate equilibrium can cause significant problems, including neurodevelopmental and neuropsychiatric disorders, such as schizophrenia and intellectual disability.

One key regulator of activity at the synapse is a protein called Bcl11b, which has been linked to conditions affected by synaptic dysfunction. It plays a critical role in maintaining specific junctions known as mossy fibre synapses, which are important for learning and memory. One of the genes regulated by Bcl11b is C1ql2, which encodes for a synaptic protein. However, it is unclear what molecular mechanisms Bcl11b uses to carry out this role.

To address this, Koumoundourou et al. explored the role of C1ql2 in mossy fibre synapses of adult mice. Experiments to manipulate the production of C1ql2 independently of Bcl11b revealed that C1ql2 is vital for recruiting vesicles to the synapse and strengthening synaptic connections between neurons. Further investigation showed that C1ql2’s role in this process relies on interacting with another synaptic protein called neurexin-3. Disrupting this interaction reduced the amount of C1ql2 at the synapse and, consequently, impaired vesicle recruitment.

These findings will help our understanding of how neurodevelopmental and neuropsychiatric disorders develop. Bcl11b, C1ql2 and neurexin-3 have been independently associated with these conditions, and the now-revealed interactions between these proteins offer new insights into the molecular basis of synaptic faults. This research opens the door to further study of how these proteins interact and their roles in brain health and disease.

Disruptions in synaptic structure and function have been identified as a major determinant in the manifestation of various neurodevelopmental and neuropsychiatric disorders, such as autism spectrum disorder, schizophrenia, and intellectual disability (Hayashi-Takagi, 2017; Lepeta et al., 2016; Zoghbi and Bear, 2012). The need to understand how synaptic function is compromised in these disorders has accentuated the importance of studying the regulatory mechanisms of physiological synaptic function. These mechanisms involve cell adhesion molecules at both the pre- and post-synaptic side that act as synaptic organizers, whose unique combination determines the structural and functional properties of the synapse. Many such proteins have already been identified and our understanding of their complex role in synapse assembly and function has significantly increased over the last years (de Wit and Ghosh, 2016; O’Rourke et al., 2012; Südhof, 2017). Furthermore, recent advances in the genetics of neurodevelopmental and neuropsychiatric disorders have implicated genes encoding for several of the known synaptic proteins, supporting a role for these molecules in the pathogenesis of corresponding disorders (Südhof, 2021; Torres et al., 2017; Wang et al., 2018).

The sensitivity of the functional specification of the synapse to the combination of distinct synaptic proteins and their relative expression levels suggests that genetically encoded programs define at least facets of the synaptic properties in a cell-type-specific manner (Südhof, 2017). Several of the synaptic proteins have been shown to promote formation of functional pre- and postsynaptic assemblies when presented in non-neuronal cells (Dalva et al., 2000; Dean et al., 2003; Scheiffele et al., 2000), showing that their ability to specify synapses is in part independent of signaling processes and neuronal activity and supporting the idea that synaptic function is governed by cues linked to cellular origin (Gomez et al., 2021). Thus, the investigation of synaptic organizers and their function in health and disease should be expanded to the transcriptional programs that regulate their expression.

Bcl11b (also known as Ctip2) is a zinc finger transcription factor that has been implicated in various disorders of the nervous system including Alzheimer’s and Huntington’s disease, and schizophrenia (Kunkle et al., 2016; Song et al., 2022; Whitton et al., 2018; Whitton et al., 2016). Patients with BCL11B mutations present with neurodevelopmental delay, overall learning deficits as well as impaired speech acquisition and autistic features (Eto et al., 2022; Lessel et al., 2018; Punwani et al., 2016; Yang et al., 2020). Bcl11b is expressed in several neuron types, including the dentate gyrus granule neurons (DGN) of the hippocampus. Expression of Bcl11b in the DGN starts during embryonic development and persists into adulthood (Simon et al., 2020). We have previously demonstrated that Bcl11b plays a crucial role in the development of the hippocampal mossy fiber system, adult hippocampal neurogenesis as well as hippocampal learning and memory (Simon et al., 2016; Simon et al., 2012). In the mature hippocampus, Bcl11b is critical for the structural and functional integrity of mossy fiber synapses (MFS), the connections between DGN and CA3 pyramidal neurons (De Bruyckere et al., 2018). MFS have a critical role in learning and memory stemming from their unique structural and functional properties, such as an enormous pool of releasable synaptic vesicles (SV), and reliable presynaptic short- and long-term plasticity (Nicoll and Schmitz, 2005; Rollenhagen and Lübke, 2010). Conditional ablation of Bcl11b in murine DGN impairs presynaptic recruitment of SV and abolishes mossy fiber long-term potentiation (MF-LTP; De Bruyckere et al., 2018). The molecular mechanisms, however, through which the transcriptional regulator Bcl11b controls highly dynamic properties of the MFS remained elusive.

In the present study, we show that the secreted synaptic organizer molecule C1ql2, a member of the C1q-like protein family (Yuzaki, 2017), is a functional target of Bcl11b in murine DGN. Reintroduction of C1ql2 in Bcl11b mutant DGN rescued the localization and docking of SV to the active zone (AZ), as well as MF-LTP that was abolished upon Bcl11b ablation. Knock-down (KD) of C1ql2 in wildtype animals recapitulated a major part of the MFS phenotype observed in Bcl11b mutants. Furthermore, we show that C1ql2 requires direct interaction with a specific neurexin-3 isoform, Nrxn3(25b+), a member of a polymorphic family of presynaptic cell adhesion molecules (Reissner et al., 2013; Südhof, 2017), to recruit SV in vitro and in vivo. Finally, we observe that localization of C1ql2 along the mossy fiber tract depends on C1ql2-Nrxn3(25b+) interaction. Taken together, this study identifies a novel Bcl11b/C1ql2/Nrxn3(25b+)-dependent regulatory mechanism that is essential for the control of MFS function. Recent genetic studies suggested its single components to be associated with neurodevelopmental and neuropsychiatric disorders characterized by synaptic dysfunction. Our data, for the first time, demonstrate these molecules to be interconnected in one regulatory pathway. Thus, our findings provide new mechanistic insight into the pathogenesis of corresponding human disorders.

There is emerging evidence that the zinc finger transcription factor Bcl11b is involved in the pathogenesis of neurodevelopmental as well as neuropsychiatric disorders that are frequently associated with synaptic dysfunction. Previous work from our group demonstrated Bcl11b to be essential for synapse function in the mossy fiber circuit of the adult murine hippocampus. The underlying molecular mechanisms downstream of Bcl11b, however, remained elusive. In the present study, we uncover a novel C1ql2-dependent regulatory pathway through which Bcl11b controls the structural as well as functional integrity of hippocampal MFS in adult mice. We show that SV recruitment to the AZ of MFS, as well as the expression of MF-LTP, depend on C1ql2, which is a direct functional target of Bcl11b. Reintroduction of C1ql2 into Bcl11b mutant DGN restores defective SV recruitment and LTP expression. KD of C1ql2 in DGN recapitulates the impaired SV recruitment and loss of LTP observed in Bcl11b mutants. Finally, we show that C1ql2 controls SV recruitment through a direct interaction with presynaptic Nrxn3(25b+), while LTP depends on C1ql2 signals independent of Nrxn3 interaction. Recent studies suggested Nrxn3, as well as C1ql2, to be associated with neuropsychiatric disorders (Hishimoto et al., 2007; Hu et al., 2013; Huggett and Stallings, 2020a; Marballi et al., 2022). Our study for the first time identifies a Bcl11b/C1ql2/Nrxn3-dependent signaling pathway in the control of basic structural and functional properties of MFS. Analysis of this regulatory pathway in mice may provide important novel insights into the pathogenesis of neurodevelopmental and neuropsychiatric disorders.

We have previously shown that conditional ablation of Bcl11b in the adult hippocampus leads to structural and functional changes of MFS characterized by an overall reduction in synapse numbers, loss of bouton complexity, misdistribution of SV as well as loss of MF-LTP (De Bruyckere et al., 2018). Here, we found that reintroduction of the synaptic organizer protein C1ql2, which is a direct transcriptional target of Bcl11b and is downregulated in Bcl11b mutant DGN (De Bruyckere et al., 2018), was able to rescue major part of the Bcl11b mutant phenotype at the MFS. Restoring C1ql2 expression in Bcl11b cKO DGN led to a complete rescue of the SV distribution and docking, as well as LTP at the MFS, while synapse numbers and ultrastructural complexity of boutons remained unchanged. Furthermore, KD of C1ql2 in WT DGN recapitulated the Bcl11b phenotype with impaired SV recruitment and loss of LTP, supporting the specificity of C1ql2 function. MF-LTP, which manifests as a long-term increase in presynaptic vesicle release probability (P_r) (Shahoha et al., 2022), directly depends on the distribution of SV in the proximity of the AZ. Recent studies have shown that the increase in P_r involves the recruitment of new AZ and an increase in the number of docked and tethered vesicles, corresponding to the readily releasable pool of SV (Orlando et al., 2021; Vandael et al., 2020). The perturbed SV recruitment in both Bcl11b cKO and C1ql2 KD mice could thus potentially explain the loss of LTP in both conditions. Indeed, the reintroduction of C1ql2 in Bcl11b cKO DGN specifically rescued SV recruitment and LTP, while synapse numbers and ultrastructural complexity of MFB remained unchanged. Whether the regulation of SV distribution by C1ql2 and the expression of MF-LTP are directly and causally linked remains to be determined. Additional factors have been suggested to contribute to the increase in P_r, including a tighter coupling between Ca²⁺ channels and SV (Midorikawa and Sakaba, 2017) and the accumulation of Ca²⁺ channels near release sites (Fukaya et al., 2021). It cannot, therefore, be excluded that C1ql2 regulates MF-LTP through one of these alternative mechanisms. Aiming to narrow in on the nature of the mechanism through which Bcl11b regulates MF-LTP, we used forskolin to induce LTP in Bcl11b cKO. MF-LTP relies on presynaptic mechanisms (Castillo, 2012; Zalutsky and Nicoll, 1990) and is mediated by the second messenger cAMP, which is produced by AC in response to Ca²⁺ influx through voltage-gated Ca²⁺ channels (Li et al., 2007) and KARs (Lauri et al., 2001; Schmitz et al., 2003). By using forskolin to directly activate AC, we bypassed these initial steps, and still found a reduction of LTP in Bcl11b cKO mice, similarly to HFS. These results strongly suggest that the loss of LTP is caused by a process downstream of the initial presynaptic Ca²⁺ influx following stimulation. We note that, in the present experiments, we did not observe the decrease in input-output relation in Bcl11b cKO as reported in De Bruyckere et al., 2018. After excluding technical differences, e.g., different methods of data analysis, we conclude that the discrepancy is best explained by differences in the population of presynaptic fibers. In the present study, mossy fiber responses were specifically identified by testing for frequency facilitation and sensitivity to mGluR antagonists, whereas in the previous study, this purification was not done (De Bruyckere et al., 2018). It is not immediately obvious why the reduction in synapse numbers and misdistribution of SV in Bcl11b cKO animals does not affect basal synaptic transmission. While a modest displacement of SV might fail to noticeably influence synaptic transmission due to the low initial P_r at MFS, causing only a fraction of release-ready vesicles to be initially released, the reduction in synapse numbers might indeed be expected to reflect in the input-output relationship. It might be that synapses that are preferentially eliminated in Bcl11b mutants are predominantly silent or have weak coupling strength, such that their loss has only a minimal effect on synaptic transmission. Further investigation is needed to elucidate this apparent discrepancy. Together, our results suggest Bcl11b to be an important synaptic regulator that controls the structure and function of adult MFS through both C1ql2-dependent, as well as -independent transcriptional programs.

C1ql proteins are complement-related factors that are synthesized by the presynapse and secreted into the synaptic cleft. Within the hippocampus, C1ql2 and –3 protein expression overlaps and is highly restricted to DGN (Iijima et al., 2010) and the corresponding mossy fiber system, including MF-CA3 synapses. C1ql2 and –3 were previously suggested to form functional heteromers that can cluster postsynaptic KAR on MFS. Selective deletion of either C1ql2 or –3 in mice was reported to have no overt mutant hippocampal phenotype, suggesting functional compensation for both proteins (Matsuda et al., 2016). Using shRNA-mediated selective KD of C1ql2 in DGN as well as rescue of the Bcl11b mutation by the reintroduction of C1ql2 into mutant DGN, we observed a novel, presynaptic function for C1ql2 in the recruitment of SV and the expression of LTP in MFS. This function was specific to C1ql2 since overexpression of C1ql3 in Bcl11b mutant DGN was unable to rescue the synapse phenotype. Furthermore, another study has identified all four C1ql proteins, including C1ql2, as ligands for the postsynaptic Brain-specific angiogenesis inhibitor 3 (BAI3). Addition of any of the four C1ql proteins to cultured hippocampal neurons led to a loss of excitatory synapses, a function inhibited by the presence of BAI3 (Bolliger et al., 2011). In our study, we show that neither loss of C1ql2 nor overexpression of C1ql2 affects the number of MFS, supporting the notion that synaptic organizers have synapse-specific functions. This highlights the role of C1ql2 as a synaptic organizer and adds a new layer of understanding to its function at the MFS.

Previous in vitro studies suggested that C1ql2 function at the MFS involves interaction with Nrxn3 isoforms containing the splice site 5 25b sequence (SS5^25b) (Matsuda et al., 2016). Nrxns are synaptic cell adhesion molecules that mediate various synaptic properties (Reissner et al., 2013; Südhof, 2017), including the recruitment of SV and dense-core vesicles (Dean et al., 2003; Ferdos et al., 2021; Quinn et al., 2017; Rui et al., 2017). This prompted us to analyze, whether C1ql2-dependent SV recruitment in MFS requires a direct interaction with Nrxn3(25b+) in vitro and in vivo. Expression of C1ql2 in HEK293 cells co-cultured with GFP-Nrxn3α(25+)-expressing hippocampal neurons was able to recruit Nrxn3α(25b+) and vGlut1 at contact points, while C1ql2.K262E, a C1ql2 variant with an amino-acid replacement that perturbs the interaction with Nrxn3(25b+), was no longer able to recruit neuronal vGlut1. Furthermore, clustering of vGlut1 by C1ql2-secreting HEK293 cells was reduced in neurons harboring a pan-neurexin mutation, a phenotype that was rescued by the selective reintroduction of Nrxn3α(25b+). Finally, the introduction of C1ql2.K262E in Bcl11b cKO DGN in vivo was unable to rescue SV recruitment, while the silencing of Nrxns in DGN in vivo perturbed SV recruitment to a similar extent as in Bcl11b cKO and C1ql2 KD. Based on these findings, we anticipated the overexpression of C1ql2.K262E in Bcl11b cKO DGN to be unable to rescue MF-LTP. Unexpectedly, the introduction of C1ql2.K262E into Bcl11b cKO fully rescued MF-LTP. This raises the possibility that C1ql2 can influence MF-LTP through additional, yet uncharacterized mechanisms, independent of SV recruitment or direct interaction with Nrxn3(25b+). We cannot exclude, however, that the expression of a mutant C1ql2 variant created an additional gain-of-function effect that circumvented SV recruitment and allowed the rescue of MF-LTP in our experimental system. The latter is supported by the fact that within the first 10 min after HFS, fEPSP slopes for C1ql2.K262E were significantly elevated compared to controls, an effect that was not seen after C1ql2 re-expression. Together, our data provide comprehensive experimental evidence that the direct interaction of C1ql2 with Nrxn3(25b+) is essential for SV recruitment at the MFS. Finally, we observed that an abolished interaction between C1ql2 and Nrxn3(25b+) was associated with reduced localization of the C1ql2 protein along the MF tract. This raises the possibility that C1ql2-Nrxn3 interaction might be involved in surface presentation of C1ql2, transportation, or stabilization at the MFS. The C1q domain can form stable, higher order oligomers (Ressl et al., 2015). Neurexins, on the other hand, are highly mobile outside and inside of synaptic terminals (Klatt et al., 2021; Neupert et al., 2015). Thus, the interaction of C1ql2 with Nrxn3(25b+) may reciprocally augment the accumulation of both proteins at synaptic sites.

Neurexin mRNAs are subjected to extensive alternative splicing that leads to the expression of thousands of isoforms with differential expression patterns (Treutlein et al., 2014; Ullrich et al., 1995) that act in a type-specific manner on synaptic functions (Dai et al., 2019; Schreiner et al., 2014; Traunmüller et al., 2016). Nrxn3 splice variants have been shown to regulate the function and plasticity of glutamatergic and GABAergic synapses through various mechanisms (Aoto et al., 2013; Dai et al., 2019; Lloyd et al., 2023; Trotter et al., 2023). The Nrxn3 splice site SS5 is a major contributor to the high number of Nrxn3 isoforms (Schreiner et al., 2014). One such isoform was recently found to be highly expressed in GABAergic interneurons at the DG, where it regulates dendritic inhibition (Hauser et al., 2022). Our findings on the role of Nrxn3 isoforms containing SS5^25b in the recruitment of SV at the MFS through interaction with C1ql2 add to the understanding of the synapse-specific mechanisms of action of Nrxns.

Perturbations in synaptic structure and function are major determinants of various neuropsychiatric and neurodevelopmental disorders (Hayashi-Takagi, 2017; Lepeta et al., 2016; Zoghbi and Bear, 2012). Emerging evidence from recent genetic studies suggests such disorders to be linked to various genes encoding for synaptic proteins (Südhof, 2021; Torres et al., 2017; Wang et al., 2018). Decoding the molecular mechanisms of synaptic organization and stability and their transcriptional regulation would therefore be expected to contribute to the mechanistic understanding of neuropsychiatric and neurodevelopmental disorders. The transcription factor Bcl11b has been linked to neurodevelopmental (Lessel et al., 2018), neurodegenerative (Kunkle et al., 2016; Song et al., 2022) and neuropsychiatric disorders (Whitton et al., 2018; Whitton et al., 2016). BCL11B mutations in humans are associated with neurodevelopmental delay, overall learning deficits as well as impaired speech acquisition and autistic features (Eto et al., 2022; Lessel et al., 2018; Punwani et al., 2016; Yang et al., 2020). Moreover, conditional ablation of Bcl11b selectively in the adult murine hippocampus results in impaired learning and memory behavior (Simon et al., 2016). NRXN3 single-nucleotide polymorphisms (SNP) have been implicated in schizophrenia (Hu et al., 2013) and addiction (Hishimoto et al., 2007), with one recorded SNP located close to SS5 altering the expression of Nrxn3(25b+). Interestingly, recent studies have also associated C1QL2 with schizophrenia (Marballi et al., 2022) as well as cocaine addiction (Huggett and Stallings, 2020b). In this study we demonstrate that Bcl11b, through its transcriptional target C1ql2, modulates the synaptic organization of MFS by controlling the recruitment of SV at AZ. This regulatory mechanism depends on a direct interaction of C1ql2 with Nrxn3(25b+). Importantly, SV trafficking and altered release probability have been implicated in neurological and neuropsychiatric disorders (Egbujo et al., 2016; Lepeta et al., 2016; Zhu et al., 2021). Thus, the identification of the Bcl11b/C1ql2/Nrxn3(25b+)-dependent signaling module in this study provides a new entry point for future mechanistic analyses of synaptopathies. Moreover, the existence of such cell-type-specific signaling modules reveals how a fundamental transcription factor with diverse functions such as Bcl11b can be implicated in the pathogenesis of brain disorders characterized by synaptic dysfunction.

All data generated or analysed during this study are included in the manuscript and supporting files; source data files have been provided for all Figures.

1. 1. Aoto J
   2. Ting P
   3. Maghsoodi B
   4. Xu N
   5. Henkemeyer M
   6. Chen L

   (2007) Postsynaptic ephrinB3 promotes shaft glutamatergic synapse formation

   The Journal of Neuroscience 27:7508–7519.

   https://doi.org/10.1523/JNEUROSCI.0705-07.2007

   • PubMed
   • Google Scholar
2. 1. Aoto J
   2. Martinelli DC
   3. Malenka RC
   4. Tabuchi K
   5. Südhof TC

   (2013) Presynaptic neurexin-3 alternative splicing trans-synaptically controls postsynaptic AMPA receptor trafficking

   Cell 154:75–88.

   https://doi.org/10.1016/j.cell.2013.05.060

   • PubMed
   • Google Scholar
3. 1. Bischofberger J
   2. Engel D
   3. Li L
   4. Geiger JRP
   5. Jonas P

   (2006) Patch-clamp recording from mossy fiber terminals in hippocampal slices

   Nature Protocols 1:2075–2081.

   https://doi.org/10.1038/nprot.2006.312

   • PubMed
   • Google Scholar
4. 1. Bolliger MF
   2. Martinelli DC
   3. Südhof TC

   (2011) The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins

   PNAS 108:2534–2539.

   https://doi.org/10.1073/pnas.1019577108

   • PubMed
   • Google Scholar
5. 1. Castillo PE

   (2012) Presynaptic LTP and LTD of excitatory and inhibitory synapses

   Cold Spring Harbor Perspectives in Biology 4:a005728.

   https://doi.org/10.1101/cshperspect.a005728

   • PubMed
   • Google Scholar
6. 1. Chen LY
   2. Jiang M
   3. Zhang B
   4. Gokce O
   5. Südhof TC

   (2017) Conditional deletion of all neurexins defines diversity of essential synaptic organizer functions for neurexins

   Neuron 94:611–625.

   https://doi.org/10.1016/j.neuron.2017.04.011

   • PubMed
   • Google Scholar
7. 1. Dai J
   2. Aoto J
   3. Südhof TC

   (2019) Alternative splicing of presynaptic neurexins differentially controls postsynaptic NMDA and AMPA receptor responses

   Neuron 102:993–1008.

   https://doi.org/10.1016/j.neuron.2019.03.032

   • PubMed
   • Google Scholar
8. 1. Dalva MB
   2. Takasu MA
   3. Lin MZ
   4. Shamah SM
   5. Hu L
   6. Gale NW
   7. Greenberg ME

   (2000) EphB receptors interact with NMDA receptors and regulate excitatory synapse formation

   Cell 103:945–956.

   https://doi.org/10.1016/s0092-8674(00)00197-5

   • PubMed
   • Google Scholar
9. 1. De Bruyckere E
   2. Simon R
   3. Nestel S
   4. Heimrich B
   5. Kätzel D
   6. Egorov AV
   7. Liu P
   8. Jenkins NA
   9. Copeland NG
   10. Schwegler H
   11. Draguhn A
   12. Britsch S

   (2018) Stability and function of hippocampal mossy fiber synapses depend on Bcl11b/Ctip2

   Frontiers in Molecular Neuroscience 11:103.

   https://doi.org/10.3389/fnmol.2018.00103

   • PubMed
   • Google Scholar
10. 1. de Wit J
    2. Ghosh A

    (2016) Specification of synaptic connectivity by cell surface interactions

    Nature Reviews. Neuroscience 17:22–35.

    https://doi.org/10.1038/nrn.2015.3

    • PubMed
    • Google Scholar
11. 1. Dean C
    2. Scholl FG
    3. Choih J
    4. DeMaria S
    5. Berger J
    6. Isacoff E
    7. Scheiffele P

    (2003) Neurexin mediates the assembly of presynaptic terminals

    Nature Neuroscience 6:708–716.

    https://doi.org/10.1038/nn1074

    • Google Scholar
12. 1. Egbujo CN
    2. Sinclair D
    3. Hahn CG

    (2016) Dysregulations of synaptic vesicle trafficking in schizophrenia

    Current Psychiatry Reports 18:77.

    https://doi.org/10.1007/s11920-016-0710-5

    • PubMed
    • Google Scholar
13. 1. Eto K
    2. Machida O
    3. Yanagishita T
    4. Shimojima Yamamoto K
    5. Chiba K
    6. Aihara Y
    7. Hasegawa Y
    8. Nagata M
    9. Ishihara Y
    10. Miyashita Y
    11. Asano Y
    12. Nagata S
    13. Yamamoto T

    (2022) Novel BCL11B truncation variant in a patient with developmental delay, distinctive features, and early craniosynostosis

    Human Genome Variation 9:43.

    https://doi.org/10.1038/s41439-022-00220-x

    • PubMed
    • Google Scholar
14. 1. Ferdos S
    2. Brockhaus J
    3. Missler M
    4. Rohlmann A

    (2021) Deletion of β-Neurexins in Mice alters the distribution of dense-core vesicles in presynapses of hippocampal and cerebellar neurons

    Frontiers in Neuroanatomy 15:757017.

    https://doi.org/10.3389/fnana.2021.757017

    • PubMed
    • Google Scholar
15. 1. Fremeau RT
    2. Kam K
    3. Qureshi T
    4. Johnson J
    5. Copenhagen DR
    6. Storm-Mathisen J
    7. Chaudhry FA
    8. Nicoll RA
    9. Edwards RH

    (2004) Vesicular glutamate transporters 1 and 2 target to functionally distinct synaptic release sites

    Science 304:1815–1819.

    https://doi.org/10.1126/science.1097468

    • Google Scholar
16. 1. Fukaya R
    2. Maglione M
    3. Sigrist SJ
    4. Sakaba T

    (2021) Rapid Ca²⁺ channel accumulation contributes to cAMP-mediated increase in transmission at hippocampal mossy fiber synapses

    PNAS 118:e2016754118.

    https://doi.org/10.1073/pnas.2016754118

    • PubMed
    • Google Scholar
17. 1. Gomez AM
    2. Traunmüller L
    3. Scheiffele P

    (2021) Neurexins: molecular codes for shaping neuronal synapses

    Nature Reviews. Neuroscience 22:137–151.

    https://doi.org/10.1038/s41583-020-00415-7

    • PubMed
    • Google Scholar
18. 1. Haas HL
    2. Schaerer B
    3. Vosmansky M

    (1979) A simple perfusion chamber for the study of nervous tissue slices in vitro

    Journal of Neuroscience Methods 1:323–325.

    https://doi.org/10.1016/0165-0270(79)90021-9

    • Google Scholar
19. 1. Hauser D
    2. Behr K
    3. Konno K
    4. Schreiner D
    5. Schmidt A
    6. Watanabe M
    7. Bischofberger J
    8. Scheiffele P

    (2022) Targeted proteoform mapping uncovers specific Neurexin-3 variants required for dendritic inhibition

    Neuron 110:2094–2109.

    https://doi.org/10.1016/j.neuron.2022.04.017

    • PubMed
    • Google Scholar
20. 1. Hayashi-Takagi A

    (2017) Synapse pathology and translational applications for schizophrenia

    Neuroscience Research 114:3–8.

    https://doi.org/10.1016/j.neures.2016.09.001

    • PubMed
    • Google Scholar
21. 1. Hishimoto A
    2. Liu QR
    3. Drgon T
    4. Pletnikova O
    5. Walther D
    6. Zhu XG
    7. Troncoso JC
    8. Uhl GR

    (2007) Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms

    Human Molecular Genetics 16:2880–2891.

    https://doi.org/10.1093/hmg/ddm247

    • PubMed
    • Google Scholar
22. 1. Hu X
    2. Zhang J
    3. Jin C
    4. Mi W
    5. Wang F
    6. Ma W
    7. Ma C
    8. Yang Y
    9. Li W
    10. Zhang H
    11. Du B
    12. Li K
    13. Liu C
    14. Wang L
    15. Lu T
    16. Zhang H
    17. Lv L
    18. Zhang D
    19. Yue W

    (2013) Association study of NRXN3 polymorphisms with schizophrenia and risperidone-induced bodyweight gain in Chinese Han population

    Progress in Neuro-Psychopharmacology & Biological Psychiatry 43:197–202.

    https://doi.org/10.1016/j.pnpbp.2012.12.007

    • PubMed
    • Google Scholar
23. 1. Huggett SB
    2. Stallings MC

    (2020a) Cocaine’omics: Genome-wide and transcriptome-wide analyses provide biological insight into cocaine use and dependence

    Addiction Biology 25:e12719.

    https://doi.org/10.1111/adb.12719

    • PubMed
    • Google Scholar
24. 1. Huggett SB
    2. Stallings MC

    (2020b) Genetic architecture and molecular neuropathology of human cocaine addiction

    The Journal of Neuroscience 40:5300–5313.

    https://doi.org/10.1523/JNEUROSCI.2879-19.2020

    • PubMed
    • Google Scholar
25. 1. Iijima T
    2. Miura E
    3. Watanabe M
    4. Yuzaki M

    (2010) Distinct expression of C1q-like family mRNAs in mouse brain and biochemical characterization of their encoded proteins

    The European Journal of Neuroscience 31:1606–1615.

    https://doi.org/10.1111/j.1460-9568.2010.07202.x

    • PubMed
    • Google Scholar
26. 1. Jurrus E
    2. Engel D
    3. Star K
    4. Monson K
    5. Brandi J
    6. Felberg LE
    7. Brookes DH
    8. Wilson L
    9. Chen J
    10. Liles K
    11. Chun M
    12. Li P
    13. Gohara DW
    14. Dolinsky T
    15. Konecny R
    16. Koes DR
    17. Nielsen JE
    18. Head-Gordon T
    19. Geng W
    20. Krasny R
    21. Wei G-W
    22. Holst MJ
    23. McCammon JA
    24. Baker NA

    (2018) Improvements to the APBS biomolecular solvation software suite

    Protein Science 27:112–128.

    https://doi.org/10.1002/pro.3280

    • PubMed
    • Google Scholar
27. 1. Klatt O
    2. Repetto D
    3. Brockhaus J
    4. Reissner C
    5. El Khallouqi A
    6. Rohlmann A
    7. Heine M
    8. Missler M

    (2021) Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior

    Cell Reports 35:109266.

    https://doi.org/10.1016/j.celrep.2021.109266

    • PubMed
    • Google Scholar
28. 1. Kunkle BW
    2. Jaworski J
    3. Barral S
    4. Vardarajan B
    5. Beecham GW
    6. Martin ER
    7. Cantwell LS
    8. Partch A
    9. Bird TD
    10. Raskind WH
    11. DeStefano AL
    12. Carney RM
    13. Cuccaro M
    14. Vance JM
    15. Farrer LA
    16. Goate AM
    17. Foroud T
    18. Mayeux RP
    19. Schellenberg GD
    20. Haines JL
    21. Pericak-Vance MA

    (2016) Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer’s disease

    Alzheimer’s & Dementia 12:2–10.

    https://doi.org/10.1016/j.jalz.2015.05.020

    • PubMed
    • Google Scholar
29. 1. Kusick GF
    2. Ogunmowo TH
    3. Watanabe S

    (2022) Transient docking of synaptic vesicles: implications and mechanisms

    Current Opinion in Neurobiology 74:102535.

    https://doi.org/10.1016/j.conb.2022.102535

    • PubMed
    • Google Scholar
30. 1. Lauri SE
    2. Bortolotto ZA
    3. Bleakman D
    4. Ornstein PL
    5. Lodge D
    6. Isaac JT
    7. Collingridge GL

    (2001) A critical role of A facilitatory presynaptic kainate receptor in mossy fiber LTP

    Neuron 32:697–709.

    https://doi.org/10.1016/s0896-6273(01)00511-6

    • PubMed
    • Google Scholar
31. 1. Lepeta K
    2. Lourenco MV
    3. Schweitzer BC
    4. Martino Adami PV
    5. Banerjee P
    6. Catuara-Solarz S
    7. de La Fuente Revenga M
    8. Guillem AM
    9. Haidar M
    10. Ijomone OM
    11. Nadorp B
    12. Qi L
    13. Perera ND
    14. Refsgaard LK
    15. Reid KM
    16. Sabbar M
    17. Sahoo A
    18. Schaefer N
    19. Sheean RK
    20. Suska A
    21. Verma R
    22. Vicidomini C
    23. Wright D
    24. Zhang X-D
    25. Seidenbecher C

    (2016) Synaptopathies: synaptic dysfunction in neurological disorders - A review from students to students

    Journal of Neurochemistry 138:785–805.

    https://doi.org/10.1111/jnc.13713

    • PubMed
    • Google Scholar
32. 1. Lessel D
    2. Gehbauer C
    3. Bramswig NC
    4. Schluth-Bolard C
    5. Venkataramanappa S
    6. van Gassen KLI
    7. Hempel M
    8. Haack TB
    9. Baresic A
    10. Genetti CA
    11. Funari MFA
    12. Lessel I
    13. Kuhlmann L
    14. Simon R
    15. Liu P
    16. Denecke J
    17. Kuechler A
    18. de Kruijff I
    19. Shoukier M
    20. Lek M
    21. Mullen T
    22. Lüdecke H-J
    23. Lerario AM
    24. Kobbe R
    25. Krieger T
    26. Demeer B
    27. Lebrun M
    28. Keren B
    29. Nava C
    30. Buratti J
    31. Afenjar A
    32. Shinawi M
    33. Guillen Sacoto MJ
    34. Gauthier J
    35. Hamdan FF
    36. Laberge A-M
    37. Campeau PM
    38. Louie RJ
    39. Cathey SS
    40. Prinz I
    41. Jorge AAL
    42. Terhal PA
    43. Lenhard B
    44. Wieczorek D
    45. Strom TM
    46. Agrawal PB
    47. Britsch S
    48. Tolosa E
    49. Kubisch C

    (2018) BCL11B mutations in patients affected by a neurodevelopmental disorder with reduced type 2 innate lymphoid cells

    Brain 141:2299–2311.

    https://doi.org/10.1093/brain/awy173

    • PubMed
    • Google Scholar
33. 1. Li L
    2. Bischofberger J
    3. Jonas P

    (2007) Differential gating and recruitment of P/Q-, N-, and R-type Ca2+ channels in hippocampal mossy fiber boutons

    The Journal of Neuroscience 27:13420–13429.

    https://doi.org/10.1523/JNEUROSCI.1709-07.2007

    • PubMed
    • Google Scholar
34. 1. Lloyd BA
    2. Han Y
    3. Roth R
    4. Zhang B
    5. Aoto J

    (2023) Neurexin-3 subsynaptic densities are spatially distinct from Neurexin-1 and essential for excitatory synapse nanoscale organization in the hippocampus

    Nature Communications 14:4706.

    https://doi.org/10.1038/s41467-023-40419-2

    • PubMed
    • Google Scholar
35. 1. Marballi KK
    2. Alganem K
    3. Brunwasser SJ
    4. Barkatullah A
    5. Meyers KT
    6. Campbell JM
    7. Ozols AB
    8. Mccullumsmith RE
    9. Gallitano AL

    (2022) Identification of activity-induced Egr3-dependent genes reveals genes associated with DNA damage response and schizophrenia

    Translational Psychiatry 12:320.

    https://doi.org/10.1038/s41398-022-02069-8

    • PubMed
    • Google Scholar
36. 1. Matsuda K
    2. Budisantoso T
    3. Mitakidis N
    4. Sugaya Y
    5. Miura E
    6. Kakegawa W
    7. Yamasaki M
    8. Konno K
    9. Uchigashima M
    10. Abe M
    11. Watanabe I
    12. Kano M
    13. Watanabe M
    14. Sakimura K
    15. Aricescu AR
    16. Yuzaki M

    (2016) Transsynaptic modulation of kainate receptor functions by C1q-like proteins

    Neuron 90:752–767.

    https://doi.org/10.1016/j.neuron.2016.04.001

    • PubMed
    • Google Scholar
37. 1. Midorikawa M
    2. Sakaba T

    (2017) Kinetics of releasable synaptic vesicles and their plastic changes at hippocampal mossy fiber synapses

    Neuron 96:1033–1040.

    https://doi.org/10.1016/j.neuron.2017.10.016

    • PubMed
    • Google Scholar
38. 1. Neupert C
    2. Schneider R
    3. Klatt O
    4. Reissner C
    5. Repetto D
    6. Biermann B
    7. Niesmann K
    8. Missler M
    9. Heine M

    (2015) Regulated dynamic trafficking of neurexins inside and outside of synaptic terminals

    The Journal of Neuroscience 35:13629–13647.

    https://doi.org/10.1523/JNEUROSCI.4041-14.2015

    • PubMed
    • Google Scholar
39. 1. Nicoll RA
    2. Schmitz D

    (2005) Synaptic plasticity at hippocampal mossy fibre synapses

    Nature Reviews. Neuroscience 6:863–876.

    https://doi.org/10.1038/nrn1786

    • PubMed
    • Google Scholar
40. 1. Orlando M
    2. Dvorzhak A
    3. Bruentgens F
    4. Maglione M
    5. Rost BR
    6. Sigrist SJ
    7. Breustedt J
    8. Schmitz D

    (2021) Recruitment of release sites underlies chemical presynaptic potentiation at hippocampal mossy fiber boutons

    PLOS Biology 19:e3001149.

    https://doi.org/10.1371/journal.pbio.3001149

    • PubMed
    • Google Scholar
41. 1. O’Rourke NA
    2. Weiler NC
    3. Micheva KD
    4. Smith SJ

    (2012) Deep molecular diversity of mammalian synapses: why it matters and how to measure it

    Nature Reviews. Neuroscience 13:365–379.

    https://doi.org/10.1038/nrn3170

    • PubMed
    • Google Scholar
42. 1. Punwani D
    2. Zhang Y
    3. Yu J
    4. Cowan MJ
    5. Rana S
    6. Kwan A
    7. Adhikari AN
    8. Lizama CO
    9. Mendelsohn BA
    10. Fahl SP
    11. Chellappan A
    12. Srinivasan R
    13. Brenner SE
    14. Wiest DL
    15. Puck JM

    (2016) Multisystem anomalies in severe combined immunodeficiency with mutant BCL11B

    The New England Journal of Medicine 375:2165–2176.

    https://doi.org/10.1056/NEJMoa1509164

    • PubMed
    • Google Scholar
43. 1. Quinn DP
    2. Kolar A
    3. Wigerius M
    4. Gomm-Kolisko RN
    5. Atwi H
    6. Fawcett JP
    7. Krueger SR

    (2017) Pan-neurexin perturbation results in compromised synapse stability and a reduction in readily releasable synaptic vesicle pool size

    Scientific Reports 7:42920.

    https://doi.org/10.1038/srep42920

    • PubMed
    • Google Scholar
44. 1. Reissner C
    2. Runkel F
    3. Missler M

    (2013) Neurexins

    Genome Biology 14:213.

    https://doi.org/10.1186/gb-2013-14-9-213

    • PubMed
    • Google Scholar
45. 1. Ressl S
    2. Vu BK
    3. Vivona S
    4. Martinelli DC
    5. Südhof TC
    6. Brunger AT

    (2015) Structures of C1q-like proteins reveal unique features among the C1q/TNF superfamily

    Structure 23:688–699.

    https://doi.org/10.1016/j.str.2015.01.019

    • PubMed
    • Google Scholar
46. 1. Rollenhagen A
    2. Lübke JHR

    (2010) The mossy fiber bouton: the “common” or the “unique” synapse?

    Frontiers in Synaptic Neuroscience 2:2.

    https://doi.org/10.3389/fnsyn.2010.00002

    • PubMed
    • Google Scholar
47. 1. Rui M
    2. Qian J
    3. Liu L
    4. Cai Y
    5. Lv H
    6. Han J
    7. Jia Z
    8. Xie W

    (2017) The neuronal protein Neurexin directly interacts with the Scribble-Pix complex to stimulate F-actin assembly for synaptic vesicle clustering

    The Journal of Biological Chemistry 292:14334–14348.

    https://doi.org/10.1074/jbc.M117.794040

    • PubMed
    • Google Scholar
48. 1. Scheiffele P
    2. Fan J
    3. Choih J
    4. Fetter R
    5. Serafini T

    (2000) Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons

    Cell 101:657–669.

    https://doi.org/10.1016/s0092-8674(00)80877-6

    • PubMed
    • Google Scholar
49. 1. Schindelin J
    2. Arganda-Carreras I
    3. Frise E
    4. Kaynig V
    5. Longair M
    6. Pietzsch T
    7. Preibisch S
    8. Rueden C
    9. Saalfeld S
    10. Schmid B
    11. Tinevez JY
    12. White DJ
    13. Hartenstein V
    14. Eliceiri K
    15. Tomancak P
    16. Cardona A

    (2012) Fiji: an open-source platform for biological-image analysis

    Nature Methods 9:676–682.

    https://doi.org/10.1038/nmeth.2019

    • PubMed
    • Google Scholar
50. 1. Schmittgen TD
    2. Livak KJ

    (2008) Analyzing real-time PCR data by the comparative C(T) method

    Nature Protocols 3:1101–1108.

    https://doi.org/10.1038/nprot.2008.73

    • PubMed
    • Google Scholar
51. 1. Schmitz D
    2. Mellor J
    3. Breustedt J
    4. Nicoll RA

    (2003) Presynaptic kainate receptors impart an associative property to hippocampal mossy fiber long-term potentiation

    Nature Neuroscience 6:1058–1063.

    https://doi.org/10.1038/nn1116

    • PubMed
    • Google Scholar
52. 1. Schreiner D
    2. Nguyen T-M
    3. Russo G
    4. Heber S
    5. Patrignani A
    6. Ahrné E
    7. Scheiffele P

    (2014) Targeted combinatorial alternative splicing generates brain region-specific repertoires of neurexins

    Neuron 84:386–398.

    https://doi.org/10.1016/j.neuron.2014.09.011

    • PubMed
    • Google Scholar
53. 1. Shahoha M
    2. Cohen R
    3. Ben-Simon Y
    4. Ashery U

    (2022) cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal

    Frontiers in Synaptic Neuroscience 14:861215.

    https://doi.org/10.3389/fnsyn.2022.861215

    • PubMed
    • Google Scholar
54. 1. Simon R
    2. Brylka H
    3. Schwegler H
    4. Venkataramanappa S
    5. Andratschke J
    6. Wiegreffe C
    7. Liu P
    8. Fuchs E
    9. Jenkins NA
    10. Copeland NG
    11. Birchmeier C
    12. Britsch S

    (2012) A dual function of Bcl11b/Ctip2 in hippocampal neurogenesis

    The EMBO Journal 31:2922–2936.

    https://doi.org/10.1038/emboj.2012.142

    • PubMed
    • Google Scholar
55. 1. Simon R
    2. Baumann L
    3. Fischer J
    4. Seigfried FA
    5. De Bruyckere E
    6. Liu P
    7. Jenkins NA
    8. Copeland NG
    9. Schwegler H
    10. Britsch S

    (2016) Structure-function integrity of the adult hippocampus depends on the transcription factor Bcl11b/Ctip2

    Genes, Brain, and Behavior 15:405–419.

    https://doi.org/10.1111/gbb.12287

    • PubMed
    • Google Scholar
56. 1. Simon R
    2. Wiegreffe C
    3. Britsch S

    (2020) Bcl11 Transcription Factors Regulate Cortical Development and Function

    Frontiers in Molecular Neuroscience 13:51.

    https://doi.org/10.3389/fnmol.2020.00051

    • PubMed
    • Google Scholar
57. 1. Song S
    2. Creus Muncunill J
    3. Galicia Aguirre C
    4. Tshilenge KT
    5. Hamilton BW
    6. Gerencser AA
    7. Benlhabib H
    8. Cirnaru MD
    9. Leid M
    10. Mooney SD
    11. Ellerby LM
    12. Ehrlich ME

    (2022) Postnatal Conditional Deletion of Bcl11b in Striatal Projection Neurons Mimics the Transcriptional Signature of Huntington’s Disease

    Biomedicines 10:10102377.

    https://doi.org/10.3390/biomedicines10102377

    • PubMed
    • Google Scholar
58. 1. Südhof TC

    (2017) Synaptic neurexin complexes: a molecular code for the logic of neural circuits

    Cell 171:745–769.

    https://doi.org/10.1016/j.cell.2017.10.024

    • PubMed
    • Google Scholar
59. 1. Südhof TC

    (2021) The cell biology of synapse formation

    The Journal of Cell Biology 220:e202103052.

    https://doi.org/10.1083/jcb.202103052

    • PubMed
    • Google Scholar
60. 1. Ting JT
    2. Daigle TL
    3. Chen Q
    4. Feng G

    (2014) Acute brain slice methods for adult and aging animals: application of targeted patch clamp analysis and optogenetics

    Methods in Molecular Biology 1183:221–242.

    https://doi.org/10.1007/978-1-4939-1096-0_14

    • PubMed
    • Google Scholar
61. 1. Torres VI
    2. Vallejo D
    3. Inestrosa NC

    (2017) Emerging synaptic molecules as candidates in the etiology of neurological disorders

    Neural Plasticity 2017:8081758.

    https://doi.org/10.1155/2017/8081758

    • PubMed
    • Google Scholar
62. 1. Traunmüller L
    2. Gomez AM
    3. Nguyen TM
    4. Scheiffele P

    (2016) Control of neuronal synapse specification by a highly dedicated alternative splicing program

    Science 352:982–986.

    https://doi.org/10.1126/science.aaf2397

    • PubMed
    • Google Scholar
63. 1. Treutlein B
    2. Gokce O
    3. Quake SR
    4. Südhof TC

    (2014) Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing

    PNAS 111:E1291–E1299.

    https://doi.org/10.1073/pnas.1403244111

    • PubMed
    • Google Scholar
64. 1. Trotter JH
    2. Wang CY
    3. Zhou P
    4. Nakahara G
    5. Südhof TC

    (2023) A combinatorial code of neurexin-3 alternative splicing controls inhibitory synapses via A trans-synaptic dystroglycan signaling loop

    Nature Communications 14:1771.

    https://doi.org/10.1038/s41467-023-36872-8

    • PubMed
    • Google Scholar
65. 1. Uchigashima M
    2. Cheung A
    3. Suh J
    4. Watanabe M
    5. Futai K

    (2019) Differential expression of neurexin genes in the mouse brain

    The Journal of Comparative Neurology 527:1940–1965.

    https://doi.org/10.1002/cne.24664

    • PubMed
    • Google Scholar
66. 1. Ullrich B
    2. Ushkaryov YA
    3. Südhof TC

    (1995) Cartography of neurexins: more than 1000 isoforms generated by alternative splicing and expressed in distinct subsets of neurons

    Neuron 14:497–507.

    https://doi.org/10.1016/0896-6273(95)90306-2

    • PubMed
    • Google Scholar
67. 1. Ushkaryov YA
    2. Südhof TC

    (1993) Neurexin III alpha: extensive alternative splicing generates membrane-bound and soluble forms

    PNAS 90:6410–6414.

    https://doi.org/10.1073/pnas.90.14.6410

    • PubMed
    • Google Scholar
68. 1. Vandael D
    2. Borges-Merjane C
    3. Zhang X
    4. Jonas P

    (2020) Short-term plasticity at hippocampal mossy fiber synapses is induced by natural activity patterns and associated with vesicle pool engram formation

    Neuron 107:509–521.

    https://doi.org/10.1016/j.neuron.2020.05.013

    • PubMed
    • Google Scholar
69. 1. Wang SSH
    2. Held RG
    3. Wong MY
    4. Liu C
    5. Karakhanyan A
    6. Kaeser PS

    (2016) Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking

    Neuron 91:777–791.

    https://doi.org/10.1016/j.neuron.2016.07.005

    • PubMed
    • Google Scholar
70. 1. Wang X
    2. Christian KM
    3. Song H
    4. Ming GL

    (2018) Synaptic dysfunction in complex psychiatric disorders: from genetics to mechanisms

    Genome Medicine 10:9.

    https://doi.org/10.1186/s13073-018-0518-5

    • PubMed
    • Google Scholar
71. 1. Weisskopf MG
    2. Castillo PE
    3. Zalutsky RA
    4. Nicoll RA

    (1994) Mediation of hippocampal mossy fiber long-term potentiation by cyclic AMP

    Science 265:1878–1882.

    https://doi.org/10.1126/science.7916482

    • PubMed
    • Google Scholar
72. 1. Whitton L
    2. Cosgrove D
    3. Clarkson C
    4. Harold D
    5. Kendall K
    6. Richards A
    7. Mantripragada K
    8. Owen MJ
    9. O’Donovan MC
    10. Walters J
    11. Hartmann A
    12. Konte B
    13. Rujescu D
    14. Gill M
    15. Corvin A
    16. Rea S
    17. Donohoe G
    18. Morris DW
    19. WTCCC2

    (2016) Cognitive analysis of schizophrenia risk genes that function as epigenetic regulators of gene expression

    American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 171:1170–1179.

    https://doi.org/10.1002/ajmg.b.32503

    • PubMed
    • Google Scholar
73. 1. Whitton L
    2. Apostolova G
    3. Rieder D
    4. Dechant G
    5. Rea S
    6. Donohoe G
    7. Morris DW

    (2018) Genes regulated by SATB2 during neurodevelopment contribute to schizophrenia and educational attainment

    PLOS Genetics 14:e1007515.

    https://doi.org/10.1371/journal.pgen.1007515

    • PubMed
    • Google Scholar
74. 1. Yang S
    2. Kang Q
    3. Hou Y
    4. Wang L
    5. Li L
    6. Liu S
    7. Liao H
    8. Cao Z
    9. Yang L
    10. Xiao Z

    (2020) Mutant BCL11B in a Patient With a Neurodevelopmental Disorder and T-Cell Abnormalities

    Frontiers in Pediatrics 8:544894.

    https://doi.org/10.3389/fped.2020.544894

    • PubMed
    • Google Scholar
75. 1. Yuzaki M

    (2017) The C1q complement family of synaptic organizers: not just complementary

    Current Opinion in Neurobiology 45:9–15.

    https://doi.org/10.1016/j.conb.2017.02.002

    • PubMed
    • Google Scholar
76. 1. Zalutsky RA
    2. Nicoll RA

    (1990) Comparison of two forms of long-term potentiation in single hippocampal neurons

    Science 248:1619–1624.

    https://doi.org/10.1126/science.2114039

    • PubMed
    • Google Scholar
77. 1. Zhu LJ
    2. Zhang C
    3. Chen C

    (2021) Research progress on vesicle cycle and neurological disorders

    Journal of Pharmacy & Pharmaceutical Sciences 24:400–412.

    https://doi.org/10.18433/jpps31458

    • PubMed
    • Google Scholar
78. 1. Zoghbi HY
    2. Bear MF

    (2012) Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities

    Cold Spring Harbor Perspectives in Biology 4:a009886.

    https://doi.org/10.1101/cshperspect.a009886

    • PubMed
    • Google Scholar

Author details

1. Artemis Koumoundourou

   Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany

   Contribution

   Conceptualization, Formal analysis, Investigation, Writing – original draft, Writing – review and editing

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-8917-5717

2. Märt Rannap

   Institute of Physiology and Pathophysiology, Faculty of Medicine, Heidelberg University, Heidelberg, Germany

   Contribution

   Formal analysis, Investigation, Writing – original draft

   Competing interests

   No competing interests declared

3. Elodie De Bruyckere

   Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany

   Contribution

   Investigation

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-6056-376X

4. Sigrun Nestel

   Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

   Contribution

   Investigation

   Competing interests

   No competing interests declared

5. Carsten Reissner

   Institute of Anatomy and Molecular Neurobiology, University of Münster, Münster, Germany

   Contribution

   Investigation, Methodology

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0002-5496-9971

6. Alexei V Egorov

   Institute of Physiology and Pathophysiology, Faculty of Medicine, Heidelberg University, Heidelberg, Germany

   Contribution

   Investigation

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0003-4899-8407

7. Pengtao Liu

   1. School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
   2. Centre for Translational Stem Cell Biology, Hong Kong, China

   Contribution

   Resources

   Competing interests

   No competing interests declared

8. Markus Missler

   Institute of Anatomy and Molecular Neurobiology, University of Münster, Münster, Germany

   Contribution

   Resources, Writing – original draft

   Competing interests

   No competing interests declared

   "This ORCID iD identifies the author of this article:" 0000-0001-8008-984X

9. Bernd Heimrich

   Department of Neuroanatomy, Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Freiburg, Freiburg, Germany

   Contribution

   Investigation, Methodology, Writing – original draft

   Competing interests

   No competing interests declared

10. Andreas Draguhn

    Institute of Physiology and Pathophysiology, Faculty of Medicine, Heidelberg University, Heidelberg, Germany

    Contribution

    Conceptualization, Supervision, Writing – original draft

    Competing interests

    No competing interests declared

11. Stefan Britsch

    Institute of Molecular and Cellular Anatomy, Ulm University, Ulm, Germany

    Contribution

    Conceptualization, Supervision, Funding acquisition, Writing – original draft, Writing – review and editing

    For correspondence

    stefan.britsch@uni-ulm.de

    Competing interests

    No competing interests declared

    "This ORCID iD identifies the author of this article:" 0000-0003-4379-3322

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