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Neuwirth, M. E.

Publications and source records attributed to Neuwirth, M. E..

2 recordsLinked to original sources

Neural activity in the anterior cingulate cortex is required for effort-based decision making

Adaptive decision making requires the evaluation of cost-benefit tradeoffs to guide action selection. Effort-based decision making (EBD) involves weighing predicted gains against effort costs and is disrupted in several neuropsychiatric disorders. The anterior cingulate cortex (ACC) is postulated to control effort-based choice via its role in encoding the value of overcoming effort costs in rodent EBD assays. However, temporally precise methods of manipulating neural activity have rarely been applied to EBD. We developed and validated a mouse version of the barrier T-maze EBD task, in which action selection is spatiotemporally segregated from surmounting an effortful obstacle and effort is minimally confounded with time cost. Optogenetic silencing of ACC excitatory neurons during action selection, rapidly and reversibly impaired preference to exert greater effort for a larger reward, when a less effortful alternative was available. Detailed analysis of mouse choice trajectories revealed that silencing ACC disrupts kinematics, especially prior to high effort choices. However, there were no effects on overall mobility or tendency to exert effort in non-choice assays. These findings establish causality between ACC neural activity and effortful action selection during spatial cost-benefit decision making. SIGNIFICANCE STATEMENTDisturbances in evaluating effort-based costs during decision making occur in depression, schizophrenia, addiction and Parkinsons disease. Precisely resolving the function of prefrontal brain regions in mediating these processes will reveal key loci of dysfunction and potential therapeutic intervention in these disorders.

neuroscience↗

Purkinje cell outputs selectively inhibit a subset of unipolar brush cells in the input layer of the cerebellar cortex

Circuitry of the cerebellar cortex is regionally and functionally specialized. Unipolar brush cells (UBCs), and Purkinje cell (PC) synapses made by axon collaterals in the granular layer, are both enriched in areas that control balance and eye-movement. Here we find a link between these specializations: PCs preferentially inhibit mGluR1-expressing UBCs that respond to mossy fiber inputs with long lasting increases in firing, but PCs do not inhibit mGluR1-lacking UBCs. PCs inhibit about 29% of mGluR1-expressing UBCs by activating GABAA receptors (GABAARs) and inhibit almost all mGluR1-expressing UBCs by activating GABABRs. PC to UBC synapses allow PC output to regulate the input layer of the cerebellar cortex in diverse ways. GABAAR-mediated feedback is fast, unreliable, noisy, and suited to linearizing input-output curves and decreasing gain. Slow GABABR-mediated inhibition allows elevated PC activity to sharpen the input-output transformation of UBCs, and allows dynamic inhibitory feedback of mGluR1-expressing UBCs.

neuroscience↗