# Loss of Thy1 in Cortico-Striatal Pathways Alters Response to Dopamine and Gabapentin

## TL;DR

This study shows that losing Thy1 in mice changes how dopamine and gabapentin affect brain circuits linked to movement and sensory responses, which may relate to restless legs syndrome.

## Contribution

The study reveals novel effects of Thy1 loss on dopaminergic and gabapentin responses in corticostriatal pathways and behavior.

## Key findings

- Loss of Thy1 alters dopaminergic modulation of corticostriatal neurotransmission.
- Thy1 KO mice show enhanced prepulse inhibition and altered startle response.
- Gabapentin has a stronger effect on Thy1 KO slices compared to controls.

## Abstract

Thy1, a synaptic protein, may support synaptic junction adherence. Thus, we hypothesized that loss of Thy1 may alter synaptic transmission. Our focus on the Thy1 knockout (KO) mouse model stems from the loss of Thy1 expression in individuals with Restless Legs Syndrome (RLS), a neurological disorder. This investigation aimed to determine: 1) if the absence of Thy1 affects synaptic function in the striatal region, 2) if the absence of Thy1 alters the synaptic response to dopamine and gabapentin, and 3) if the Thy1 loss can alter behavior modulated by the striatum. Network-level synaptic transmission was measured in corticostriatal slices from Thy1 KO and C57BL/6 control mice. In vivo, acoustic startle behavioral testing was used to measure startle reaction and prepulse inhibition in both groups. Raclopride, a D2 receptor antagonist, decreased population spike amplitude in control but not Thy1 KO slices. Quinpirole, a D2 receptor agonist, did not change spike amplitude in any group. Gabapentin, a Ca2+ channel blocker, reduced population spike amplitude in Thy1 KO slices more than in controls. The behavioral acoustic startle response was diminished in Thy1 KO mice and attributed to enhanced prepulse inhibition. Loss of Thy1 alters striatal synaptic function, affecting dopaminergic modulation of corticostriatal neurotransmission and resulting in disruption of the startle response and prepulse inhibition.

Loss of Thy1 affects dopaminergic modulation of corticostriatal neurotransmission.Loss of Thy1 alters the pharmacological response to dopaminergic agents and gabapentin.Loss of Thy1 affects startle response to auditory stimuli.Thy1 knockout in mice affects neural mechanisms common to restless legs syndrome.

Loss of Thy1 affects dopaminergic modulation of corticostriatal neurotransmission.

Loss of Thy1 alters the pharmacological response to dopaminergic agents and gabapentin.

Loss of Thy1 affects startle response to auditory stimuli.

Thy1 knockout in mice affects neural mechanisms common to restless legs syndrome.