A tonic nicotinic brake controls spike timing in striatal spiny projection neurons
- The Hebrew University of Jerusalem, Israel
- Stony Brook University, United States
- University College London, United Kingdom
- Karolinska Institutet, Sweden
Abstract
Striatal spiny projection neurons (SPNs) transform convergent excitatory corticostriatal inputs into an inhibitory signal that shapes basal ganglia output. This process is fine-tuned by striatal GABAergic interneurons (GINs), which receive overlapping cortical inputs and mediate rapid corticostriatal feedforward inhibition of SPNs. Adding another level of control, cholinergic interneurons (CINs), which are also vigorously activated by corticostriatal excitation, can disynaptically inhibit SPNs by activating α4β2 nicotinic acetylcholine receptors (nAChRs) on various GINs. Measurements of this disynaptic inhibitory pathway, however, indicate that it is too slow to compete with direct GIN-mediated feed-forward inhibition. Moreover, functional nAChRs are also present on populations of GINs that respond only weakly to phasic activation of CINs, such as parvalbumin-positive fast-spiking interneurons (PV-FSIs), making the overall role of nAChRs in shaping striatal synaptic integration unclear. Using acute striatal slices from mice we show that upon synchronous optogenetic activation of corticostriatal projections blockade of α4β2 nAChRs shortened SPN spike latencies and increased postsynaptic depolarizations. The nAChR-dependent inhibition was mediated by downstream GABA release, and data suggest that the GABA source was not limited to GINs that respond strongly to phasic CIN activation. In particular, the observed decrease in spike latency caused by nAChR blockade was associated with a diminished frequency of spontaneous inhibitory postsynaptic currents in SPNs, a parallel hyperpolarization of PV-FSIs, and was occluded by pharmacologically preventing cortical activation of PV-FSIs. Taken together, we describe a role for tonic (as opposed to phasic) activation of nAChRs in striatal function. We conclude that tonic activation of nAChRs by CINs maintains a GABAergic brake on cortically-driven striatal output by 'priming' feedforward inhibition, a process that may shape SPN spike timing, striatal processing and synaptic plasticity.
Data availability
All analyzed data sets, whether included in figures or referenced as 'not shown', have been uploaded to OSF and made publically available: https://osf.io/7kazd
Article and author information
Author details
Funding
BSF (2017020)
- Joshua A Goldberg
- Joshua L Plotkin
ISF (154/14)
- Joshua A Goldberg
ERC Consolidator (646880)
- Joshua A Goldberg
NIH (R01 NS104089/NINDS)
- Joshua L Plotkin
NIH (NS022061/NINDS)
- Joshua L Plotkin
Swedish Brain Fund grant (FO2021-0333)
- Gilad Silberberg
Swedish Brain Fund grant (PS2020-0020)
- Yvonne Johansson
Swedish Research Council grant (2019-01254)
- Gilad Silberberg
Wallenberg Academy Fellowship (KAW 2017.0273)
- Gilad Silberberg
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All experimental procedures on mice adhered to and received prior written approval from the Institutional Animal Care and Use Committees of the Hebrew University of Jerusalem (MD-14-14195-3 and MD-18-15657-3) and of Stony Brook University (737496) and of the local ethics committee of Stockholm, Stockholms Norra djurförsöksetiska nämnd (N2022_2020).
Copyright
© 2022, Matityahu et al.
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.
Metrics
-
- 1,642
- views
-
- 376
- downloads
-
- 10
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A tonic nicotinic brake controls spike timing in striatal spiny projection neurons
eLife 11:e75829.
https://doi.org/10.7554/eLife.75829
Further reading
-
- Neuroscience
Evidence accumulation models (EAMs) are the dominant framework for modeling response time (RT) data from speeded decision-making tasks. While providing a good quantitative description of RT data in terms of abstract perceptual representations, EAMs do not explain how the visual system extracts these representations in the first place. To address this limitation, we introduce the visual accumulator model (VAM), in which convolutional neural network models of visual processing and traditional EAMs are jointly fitted to trial-level RTs and raw (pixel-space) visual stimuli from individual subjects in a unified Bayesian framework. Models fitted to large-scale cognitive training data from a stylized flanker task captured individual differences in congruency effects, RTs, and accuracy. We find evidence that the selection of task-relevant information occurs through the orthogonalization of relevant and irrelevant representations, demonstrating how our framework can be used to relate visual representations to behavioral outputs. Together, our work provides a probabilistic framework for both constraining neural network models of vision with behavioral data and studying how the visual system extracts representations that guide decisions.
-
- Neuroscience
How and why is working memory (WM) capacity limited? Traditional cognitive accounts focus either on limitations on the number or items that can be stored (slots models), or loss of precision with increasing load (resource models). Here, we show that a neural network model of prefrontal cortex and basal ganglia can learn to reuse the same prefrontal populations to store multiple items, leading to resource-like constraints within a slot-like system, and inducing a trade-off between quantity and precision of information. Such ‘chunking’ strategies are adapted as a function of reinforcement learning and WM task demands, mimicking human performance and normative models. Moreover, adaptive performance requires a dynamic range of dopaminergic signals to adjust striatal gating policies, providing a new interpretation of WM difficulties in patient populations such as Parkinson’s disease, ADHD, and schizophrenia. These simulations also suggest a computational rather than anatomical limit to WM capacity.
