Clustered gamma-protocadherins regulate cortical interneuron programmed cell death DOI Creative Commons
Walter Mancia,

Julien Spatazza,

Benjamin Rakela

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: July 7, 2020

Cortical function critically depends on inhibitory/excitatory balance. inhibitory interneurons (cINs) are born in the ventral forebrain and migrate into cortex, where their numbers adjusted by programmed cell death. Here, we show that loss of clustered gamma protocadherins (Pcdhg), but not genes alpha or beta clusters, increased dramatically cIN BAX-dependent death mice. Surprisingly, electrophysiological morphological properties Pcdhg-deficient wild-type cINs during period were indistinguishable. Co-transplantation with interneuron precursors further reduced mutant survival, proportion cells undergoing was affected density. Transplantation also allowed us to test for contribution Pcdhg isoforms regulation We conclude Pcdhg, specifically Pcdhgc3, Pcdhgc4, Pcdhgc5, play a critical role regulating survival endogenous

Language: Английский

Heterosynaptic Plasticity Determines the Set Point for Cortical Excitatory-Inhibitory Balance DOI Creative Commons

Rachel E. Field,

James A. D’amour, Robin Tremblay

et al.

Neuron, Journal Year: 2020, Volume and Issue: 106(5), P. 842 - 854.e4

Published: March 25, 2020

Language: Английский

Citations

77
Hearing loss and brain plasticity: the hyperactivity phenomenon DOI
Björn Herrmann, Blake E. Butler

Brain Structure and Function, Journal Year: 2021, Volume and Issue: 226(7), P. 2019 - 2039

Published: June 7, 2021

Language: Английский

Citations

62
Global and subtype-specific modulation of cortical inhibitory neurons regulated by acetylcholine during motor learning DOI Creative Commons
Chi Ren, Kailong Peng,

Ruize Yang

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(14), P. 2334 - 2350.e8

Published: May 17, 2022

Language: Английский

Citations

61
Regulation of circuit organization and function through inhibitory synaptic plasticity DOI
Yue Kris Wu, Christoph Miehl, Julijana Gjorgjieva

et al.

Trends in Neurosciences, Journal Year: 2022, Volume and Issue: 45(12), P. 884 - 898

Published: Oct. 28, 2022

Language: Английский

Citations

59
Synapse-type-specific competitive Hebbian learning forms functional recurrent networks DOI Creative Commons
Samuel Eckmann, Edward Young, Julijana Gjorgjieva

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 13, 2024

Cortical networks exhibit complex stimulus–response patterns that are based on specific recurrent interactions between neurons. For example, the balance excitatory and inhibitory currents has been identified as a central component of cortical computations. However, it remains unclear how required synaptic connectivity can emerge in developing circuits where synapses neurons simultaneously plastic. Using theory modeling, we propose wide range response properties arise from single plasticity paradigm acts at all connections—Hebbian learning is stabilized by synapse-type-specific competition for limited supply resources. In plastic circuits, this enables formation decorrelation inhibition-balanced receptive fields. Networks develop an assembly structure with stronger connections similarly tuned normalization orientation-specific center-surround suppression, reflecting stimulus statistics during training. These results demonstrate self-organize into functional suggest essential role competitive development circuits.

Language: Английский

Citations

9
Mediodorsal thalamus regulates task uncertainty to enable cognitive flexibility DOI Creative Commons
Xiaohan Zhang, Arghya Mukherjee, Michael M. Halassa

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 18, 2025

The mediodorsal (MD) thalamus is a critical partner for the prefrontal cortex (PFC) in cognitive control. Accumulating evidence has shown that MD regulates task uncertainty decision making and enhance flexibility. However, computational mechanism of this process remains unclear. Here we trained biologically-constrained models to delineate mechanistic role context-dependent making. We show addition feedforward structure recurrent PFC increases robustness low cueing signal-to-noise ratio, enhances working memory, enables rapid context switching. Incorporating genetically identified thalamocortical connectivity interneuron cell types into model replicates key neurophysiological findings task-performing animals. Our reveals mechanisms geometric interpretations regulating cue switching enable makes experimentally testable predictions linking deficits with disrupted connectivity, excitation-inhibition imbalance dysfunctional inhibitory types. by which activity flexibility not fully understood. authors build incorporating Together experimental testing, circuit

Language: Английский

Citations

1
Disease-associated missense mutations in GluN2B subunit alter NMDA receptor ligand binding and ion channel properties DOI Creative Commons
Laura Fedele, Joseph Newcombe, Maya Topf

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Feb. 28, 2018

Genetic and bioinformatic analyses have identified missense mutations in GRIN2B encoding the NMDA receptor GluN2B subunit autism, intellectual disability, Lennox Gastaut West Syndromes. Here, we investigated several such using a near-complete, hybrid 3D model of human NMDAR studied their consequences with kinetic modelling electrophysiology. The mutants revealed reductions glutamate potency; increased desensitisation; ablation voltage-dependent Mg

Language: Английский

Citations

75
Understanding the computation of time using neural network models DOI Creative Commons
Zedong Bi, Changsong Zhou

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(19), P. 10530 - 10540

Published: April 27, 2020

To maximize future rewards in this ever-changing world, animals must be able to discover the temporal structure of stimuli and then anticipate or act correctly at right time. How perceive, maintain, use time intervals ranging from hundreds milliseconds multi-seconds working memory? information is processed concurrently with spatial decision making? Why there are strong neuronal signals tasks which not required? A systematic understanding underlying neural mechanisms still lacking. Here, we addressed these problems using supervised training recurrent network models. We revealed that networks perceive elapsed through state evolution along stereotypical trajectory, maintain memory monotonic increase decrease firing rates interval-tuned neurons, compare produce by scaling speed. Temporal non-temporal coded subspaces orthogonal each other, trajectories different quasi-parallel isomorphic. Such coding geometry facilitates decoding generalizability across other. The exhibits multiple feedforward sequences mutually excite inhibit depending on whether their preferences similar not. identified four factors facilitate non-timing tasks, including anticipation coming events. Our work discloses fundamental computational principles processing, supported gives predictions a number experimental phenomena.

Language: Английский

Citations

67
Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward DOI Creative Commons
Changyou Jiang,

Xueying Wang,

Qiumin Le

et al.

Molecular Psychiatry, Journal Year: 2019, Volume and Issue: 26(4), P. 1178 - 1193

Published: Aug. 14, 2019

Abstract Opioids, such as morphine, are clinic analgesics which induce euphoria. Morphine exposure modifies the excitability and functional interactions between neurons, while underlying cellular molecular mechanisms, especially how morphine assembles heterogeneous interneurons (INs) in prelimbic cortex (PrL) to mediate disinhibition reward, not clear. Using approaches of optogenetics, electrophysiology, cell type-specific RNA-seq, we show that attenuates inhibitory synaptic transmission from parvalbumin + (PV)-INs onto pyramidal neurons PrL via μ-opioid receptor (MOR) PV-INs. Meanwhile, enhances inputs somatostatin (SST)-INs PV-INs, thus disinhibits δ-opioid (DOR)-dependent Rac1 upregulation SST-INs. We MOR PV-INs is required for morphine-induced behavioral sensitization, DOR well activity SST-INs conditioned place preference hyper-locomotion. These results reveal SST- functioning a disinhibitory architecture, coordinated by different opioid receptors disinhibit enhance reward.

Language: Английский

Citations

66
Learning prediction error neurons in a canonical interneuron circuit DOI Creative Commons
Loreen Hertäg, Henning Sprekeler

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Aug. 21, 2020

Sensory systems constantly compare external sensory information with internally generated predictions. While neural hallmarks of prediction errors have been found throughout the brain, circuit-level mechanisms that underlie their computation are still largely unknown. Here, we show a well-orchestrated interplay three interneuron types shapes development and refinement negative prediction-error neurons in computational model mouse primary visual cortex. By balancing excitation inhibition multiple pathways, experience-dependent inhibitory plasticity can generate different variants circuits, which be distinguished by simulated optogenetic experiments. The experience-dependence circuit is consistent circuits layer 2/3 Our makes range testable predictions may shed light on circuitry underlying errors.

Language: Английский

Citations

59