Synaptic input sequence discrimination on behavioral time-scales mediated by reaction-diffusion chemistry in dendrites

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Abstract

Sequences of events are ubiquitous in sensory, motor, and cognitive function. Key computational operations, including pattern recognition, event prediction, and plasticity, involve neural discrimination of spatio-temporal sequences. Here we show that synaptically-driven reaction-diffusion pathways on dendrites can perform sequence discrimination on behaviorally relevant time-scales. We used abstract signaling models to show that selectivity arises when inputs at successive locations are aligned with, and amplified by, propagating chemical waves triggered by previous inputs. We incorporated biological detail using sequential synaptic input onto spines in morphologically, electrically, and chemically detailed pyramidal neuronal models based on rat data. Again, sequences were recognized, and local channel modulation downstream of putative sequence-triggered signaling could elicit changes in neuronal firing. We predict that dendritic sequence-recognition zones occupy 5 to 30 microns and recognize time-intervals of 0.2 to 5s. We suggest that this mechanism provides highly parallel and selective neural computation in a functionally important time range.

Data availability

The following previously published data sets were used

(2007) NeuroMorpho.org
Publicly available at NeuroMorpho.org (accession no: NMO_09573).

http://neuromorpho.org/neuron_info.jsp?neuron_name=VHC-neuron

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Upinder Singh Bhalla

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India

For correspondence
bhalla@ncbs.res.in

Competing interests
Upinder Singh Bhalla, Reviewing editor, eLife.

"This ORCID iD identifies the author of this article:" 0000-0003-1722-5188

Funding

National Centre for Biological Sciences (Plan 4142)

Upinder Singh Bhalla

Department of Science and Technology, Ministry of Science and Technology (SR/CSI/66/2013)

Upinder Singh Bhalla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Upinder Singh Bhalla

(2017)

Synaptic input sequence discrimination on behavioral time-scales mediated by reaction-diffusion chemistry in dendrites

eLife 6:e25827.

https://doi.org/10.7554/eLife.25827

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Research organism

1. Medicine
2. Neuroscience
Blood metabolomic profiling reveals new targets in the management of psychological symptoms associated with severe alcohol use disorder

Sophie Leclercq, Hany Ahmed ... Nathalie Delzenne

Research Article Nov 29, 2024
Background:

Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits.

Methods:

In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal.

Results:

We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue.

Conclusions:

Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD.

Funding:

Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.
1. Neuroscience
Brain Activity: Unifying networks of a rhythm

Mohsen Alavash

Insight Nov 28, 2024
Combining electrophysiological, anatomical and functional brain maps reveals networks of beta neural activity that align with dopamine uptake.
1. Neuroscience
Spinal V1 inhibitory interneuron clades differ in birthdate, projections to motoneurons, and heterogeneity

Andrew E Worthy, Joanna T Anderson ... Francisco J Alvarez

Research Article Nov 28, 2024
Spinal cord interneurons play critical roles shaping motor output, but their precise identity and connectivity remain unclear. Focusing on the V1 interneuron cardinal class we defined four major V1 subsets in the mouse according to neurogenesis, genetic lineage-tracing, synaptic output to motoneurons, and synaptic inputs from muscle afferents. Sequential neurogenesis delineates different V1 subsets: two early born (Renshaw and Pou6f2) and two late born (Foxp2 and Sp8). Early born Renshaw cells and late born Foxp2-V1 interneurons are tightly coupled to motoneurons, while early born Pou6f2-V1 and late born Sp8-V1 interneurons are not, indicating that timing of neurogenesis does not correlate with motoneuron targeting. V1 clades also differ in cell numbers and diversity. Lineage labeling shows that the Foxp2-V1 clade contains over half of all V1 interneurons, provides the largest inhibitory input to motoneuron cell bodies, and includes subgroups that differ in birthdate, location, and proprioceptive input. Notably, one Foxp2-V1 subgroup, defined by postnatal Otp expression, is positioned near the LMC and receives substantial input from proprioceptors, consistent with an involvement in reciprocal inhibitory pathways. Combined tracing of ankle flexor sensory afferents and interneurons monosynaptically connected to ankle extensors confirmed placement of Foxp2-V1 interneurons in reciprocal inhibitory pathways. Our results validate previously proposed V1 clades as unique functional subtypes that differ in circuit placement, with Foxp2-V1 cells forming the most heterogeneous subgroup. We discuss how V1 organizational diversity enables understanding of their roles in motor control, with implications for their diverse ontogenetic and phylogenetic origins.