Strengthened Inputs from Secondary Motor Cortex to Striatum in a Mouse Model of Compulsive Behavior

• DOI: 10.1523/jneurosci.1728-18.2018
• Publication Date: 2019-02-08T23:06:18Z
• Authors: Victoria L. Corbit; Elizabeth E. Manning; Aryn H. Gittis; Susanne E. Ahmari
• Keywords: Medium spiny neuron; Orbitofrontal cortex

Hyperactivity in striatum is associated with compulsive behaviors obsessive-compulsive disorder (OCD) and related illnesses, but it unclear whether this hyperactivity due to intrinsic striatal dysfunction or abnormalities corticostriatal inputs. Understanding the cellular circuit properties underlying could help inform optimization of targeted stimulation treatments for behavior disorders. To investigate synaptic that may underlie relevant OCD, we used Sapap3 knock-out ( -KO) mouse model behaviors, which also exhibits central striatum. Ex vivo electrophysiology double-transgenic mice was assess excitability functional input spiny projection neurons (SPNs) fast-spiking interneurons (FSIs) -KOs wild-type (WT) littermates. While found no differences SPNs FSIs between WTs, excitatory drive significantly increased KOs. Contrary predictions, lateral orbitofrontal cortex-striatal synapses were not responsible drive; optogenetic revealed cortex reduced KOs (∼3-fold) unchanged FSIs. However, secondary motor area (M2) postsynaptic responses (∼6-fold) strength reliability relative WTs. These results suggest M2-striatal contribute both support a potential role presupplementary/supplementary cortical regions pathology treatment SIGNIFICANCE STATEMENT findings highlight an unexpected contribution M2 projections -KO (OCD)-relevant model, inputs strengthened by at least sixfold onto Because thought be homologous areas (pre-SMA/SMA) humans, important movement preparation behavioral sequencing, these data are consistent from leads excessive selection sequenced patterns. Together observations pre-SMA/SMA OCD Tourette syndrome, evidence pre-SMA target repetitive transcranial magnetic further dissection compulsivity.