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Gjoni, E.

Publications and source records attributed to Gjoni, E..

2 recordsLinked to original sources

Complementary cortical and thalamic contributions to cell-type-specific striatal activity dynamics during movement

Coordinated motor behavior emerges from information flow across brain regions. How long-range inputs drive cell-type-specific activity within motor circuits remains unclear. The dorsolateral striatum (DLS) contains direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) with distinct roles in movement control. In mice performing skilled locomotion, we recorded from dMSNs, iMSNs, and their cortical and thalamic inputs identified by monosynaptic rabies tracing. An RNN classifier and clustering analysis revealed functionally heterogeneous subpopulations in each population, with dMSNs preferentially activated at movement onset and offset, and iMSNs during execution. Cortical and thalamic inputs were preferentially activated during onset/offset and execution, respectively, though dMSN- and iMSN-projecting neurons in each region showed similar patterns. Locomotion phase-specific rhythmic activity was found in a subset of thalamic dMSN-projecting neurons and dMSNs. Cortex or thalamus inactivation reduced MSN activity. These findings suggest that corticostriatal and thalamostriatal inputs convey complementary motor signals via shared and cell-type-specific pathways.

neuroscience↗

Optogenetic restoration of neuron subtype-specific cortical activity ameliorates motor deficits in Huntington's Disease mice

Huntingtons disease (HD) is a devastating movement disorder without a current cure. Although the monogenic basis of HD is well-defined, the complex downstream effects that underlie behavioral symptoms are poorly understood. These effects include cortical dysfunctions, yet the role of specific cortical neuronal subtypes in HD symptoms remain largely unexplored. Here, we used longitudinal in vivo two-photon calcium imaging to examine the activity of two cortical inhibitory neuron (IN) subtypes and excitatory corticostriatal projection neurons (CSPNs) in the motor cortex of R6/2 HD mouse model throughout disease progression. We found that motor deficits in R6/2 mice were accompanied by neuron type-specific abnormalities in movement-related activity, including hypoactivity of vasoactive intestinal peptide (VIP)-INs and CSPNs. Optogenetic activation of VIP-INs in R6/2 mice restored healthy levels of activity in VIP-INs and their downstream CSPNs and ameliorated motor deficits in R6/2 mice. Our findings highlight cortical INs as a potential therapeutic target for HD and possibly other neurological diseases.

neuroscience↗