[R01] Somatostatin neurons and learning
Ente: National Institute of Neurological Disorders and Stroke
Scadenza: 2031-01-31
Importo max: 455.645 EUR
Paese: US
Descrizione
ABSTRACT ___________
Somatostatin-expressing (SST) GABAergic neurons are a key component of neocortical circuits, implicated in
sensory perception, plasticity, and disease. Understanding SST function has been hampered by the diverse
transcriptional and electrophysiological profiles of this inhibitory neuronal class, with between 10 and nearly 40
different proposed subtypes. We have identified a molecularly-defined subset of SST neurons localized to
superficial layers of mouse sensory cortex that show response plasticity when sensory stimuli predict reward
outcome, but not when stimuli and rewards are uncoupled. This critical insight provides a foothold to bridge the
local network properties of specific subtypes of SST neurons with brain-scale signals involved in reinforcement
learning. Here we will define the circuit properties of this SST subtype and how they change during whisker-
dependent sensory association learning, taking advantage of cell-type and pathway-specific analysis in acute
brain slices. In parallel, we will use longitudinal Ca++ to image these SST neurons during learning, adapting our
freely-moving task to a head-fixed training paradigm. In vivo imaging will also enable us to dynamically
manipulate stimulus-reward contingencies during learning, to determine how predictive sensory input,
expectation, and surprise regulate SST response properties. Finally, based on our preliminary data that
implicates neuromodulator activity in SST response plasticity during stimulus-reward pairing, we will test the role
of cortical norepinephrine and serotonin in regulating SST activity during learning.
Istituzione: CARNEGIE-MELLON UNIVERSITY
PI: ALISON L BARTH
Progetto: 1R01NS147337-01
Settori: National Institute of Neurological Disorders and Stroke
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