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Gonzalez Montalvo, I.

Publications and source records attributed to Gonzalez Montalvo, I..

2 recordsLinked to original sources

Parvalbumin interneurons gate and shape striatal sequences

Impulsive and uncontrolled behaviors are associated with loss of parvalbumin-expressing striatal interneurons (PV+). To understand this microcircuit mechanism we compared spiking of five classes of identified neurons in sensorimotor striatum, as rats waited for a cue, then performed brief actions. During waiting PV+ increased firing, and suppression of PV+ increased premature movements, supporting a role in action restraint. Once underway, each action was accompanied by a rapid striatal firing sequence, including PV+ and direct and indirect pathway spiny projection neurons (SPNs). Nearby PV+ and SPNs showed millisecond-level synchrony, and PV+ firing inhibited SPNs ~2ms later. Suppressing PV+ immediately changed which SPNs participated in sequences, and slowed movements. PV+ thus provide both broad restraint and precise sculpting of striatal output to achieve fluid, appropriately timed behavior.

neuroscience↗

Therapeutic Deep Brain Stimulation Disrupts Subthalamic Nucleus Activity Dynamics in Parkinsonian Mice

Subthalamic nucleus deep brain stimulation (STN DBS) relieves many motor symptoms of Parkinsons Disease (PD), but its underlying therapeutic mechanisms remain unclear. Since its advent, three major theories have been proposed: (1) DBS inhibits the STN and basal ganglia output; (2) DBS antidromically activates motor cortex; and (3) DBS disrupts firing dynamics within the STN. Previously, stimulation-related electrical artifacts limited mechanistic investigations using electrophysiology. We used electrical artifact-free calcium imaging to investigate activity in basal ganglia nuclei during STN DBS in parkinsonian mice. To test whether the observed changes in activity were sufficient to relieve motor symptoms, we then combined electrophysiological recording with targeted optical DBS protocols. Our findings suggest that STN DBS exerts its therapeutic effect through the disruption of STN dynamics, rather than inhibition or antidromic activation. These results provide insight into optimizing PD treatments and establish an approach for investigating DBS in other neuropsychiatric conditions.

neuroscience↗