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Ferrigno, S. M.

Publications and source records attributed to Ferrigno, S. M..

2 recordsLinked to original sources

Striatal interneuron microcircuits gate reinforcement to stabilize adaptive choice

The dorsomedial striatum guides learning and adaptive decision-making through excitatory synaptic control of its spiny projection neuron outputs. However, the contributions of local inhibitory microcircuitry remain poorly understood. Here, we identify an interneuron circuit in the dorsomedial striatum that links outcome processing to adaptive action selection. During probabilistic push-pull reversal learning, interneurons represented immediate outcomes: somatostatin interneurons were recruited on unrewarded trials and unexpected rewarded trials, whereas tyrosine hydroxylase interneurons were suppressed on unrewarded trials and recruited on rewarded trials. In vivo recruitment of tyrosine hydroxylase interneurons suppressed somatostatin interneuron activity and increased activity in both direct- and indirect-pathway striatal projection neurons, revealing a polysynaptic disinhibitory microcircuit. Transient inhibition of somatostatin interneurons in this pull-tuned region produced a sustained increase in aberrant pull choices and occupancy of a suboptimal pull-preferring behavioral state, whereas inhibition of tyrosine hydroxylase interneurons produced a sustained impairment of pull reinforcement. Longer-term policy changes following somatostatin interneuron inhibition coincided with postsynaptic potentiation of excitatory synapses onto striatal projection neurons, suggesting a potential substrate for the persistence of altered behavioral policies. Together, these findings identify a disinhibitory striatal circuit motif gating reinforcement which transforms individual trial outcomes into temporally broader policy.

neuroscience↗

Indirect pathway neurons in the tail of the striatum regulate inhibitory control over sensory driven behavior

Inhibitory control, or the ability to withhold action in certain situations, is behaviorally essential. Disrupted inhibitory control is linked to various neuropsychiatric symptoms, making it critical to understand the underlying neural basis. We examined how the tail of the striatum (TS), a major basal ganglia sensory hub, regulates actions to sensory stimuli. Mice performed an auditory Go/NoGo task where we recorded cell-specific activity of TS neurons. Both major striatal types were active during target sounds, but non-target sounds preferentially engaged indirect pathway neurons. Temporarily silencing this activity increased errors to non-target stimuli, indicating a role in suppressing inappropriate action. In mice deficient for the synaptic adhesion molecule Neurexin1, a gene linked to autism spectrum disorder and ADHD, TS indirect pathway recruitment was reduced, and these mice demonstrated auditory-specific inhibitory control deficits. Altogether, these findings highlight a subcortical target to potentially improve attentional and behavioral regulation in neurodevelopmental disorders. TeaserPosterior striatal circuits control sensory-guided actions and are disrupted in a rodent model of neurodevelopmental disorders.

neuroscience↗