Scaria, L. K. | Search bioRxiv

bioRxiv2024

Striatal lateral inhibition regulates action selection in a mouse model of levodopa-induced dyskinesia

Striatal medium spiny neurons (MSNs) integrate convergent cortical, thalamic, and dopaminergic inputs to shape motor output. In addition, MSNs form local inhibitory synaptic connections with one another. The function of this striatal lateral inhibition is unknown, but one possibility is in selecting an intended action while suppressing alternatives. The execution of selected movements is disrupted in several movement disorders, including levodopa-induced dyskinesia (LID), a complication of Parkinsons disease (PD) therapy characterized by involuntary movements. Here, we identify chronic changes in the strength of striatal lateral inhibitory synapses in a mouse model of PD/LID. These synapses are also modulated by acute dopamine signaling. Chemogenetic suppression of lateral inhibition originating from dopamine D2 receptor-expressing MSNs lowers the threshold to develop involuntary movements in vivo. By comparing striatal lateral inhibition in health and PD/LID, our findings support a role for this microcircuit in movement selection and suggest its disruption may increase vulnerability to dyskinesia.

neuroscience↗

bioRxiv2022

Localization of chemical synapses and modulatory release sites in the cardiac ganglion of the crab, Cancer borealis

The crustacean cardiac ganglion (CG) comprises nine neurons that provide rhythmic drive to the heart. The CG is the direct target of multiple modulators. Synapsin-like immunoreactivity was found clustered around the somata of the large cells (LC) and in a neuropil at the anterior branch of the CG trunk. This implicates the soma as a key site of synaptic integration, an unusual configuration in invertebrates. Proctolin is an excitatory neuromodulator of the CG and proctolin-like immunoreactivity exhibited partial overlap with putative chemical synapses near the LCs and at the neuropil. A proctolin-like projection was also found in a pair of excitatory nerves entering the CG. GABA-like immunoreactivity was nearly completely colocalized with chemical synapses near the LCs but absent at the anterior branch neuropil. GABA-like projections were found in a pair of inhibitory nerves entering the CG. Cancer borealis Allatostatin B1 (CbAST-B1), red pigment concentrating hormone (RPCH) and FLMRFamide-like immunoreactivity each had a unique pattern of staining and co-localization with putative chemical synapses. These results provide morphological evidence that synaptic input is integrated at LC somata in the CG. Our findings provide a topographical organization for some of the multiple inhibitory and excitatory modulators that alter the rhythmic output of this semi-autonomous motor circuit.

neuroscience↗