Inhibitory inputs from thalamus promote resilient spiking in tail of striatum

Thalamic afferents form glutamatergic synapses with striatal medium spiny neurons (MSNs). These projections are involved in complex learning processes and have primarily been studied in rostral striatum. Caudal regions, such as tail of striatum (TS), have only recently gained attention. Medial geniculate body (auditory thalamus; MGB) provides functional excitatory inputs to MSNs in TS; however, it is unclear how MGB regulates striatal output signals. We therefore performed optogenetics-assisted circuit mapping in <i>ex vivo</i> brain slices to examine how MGB modulates neuronal output in TS MSNs. Whole-cell recordings revealed that activation of MGB terminals increases MSN firing specifically at high levels of postsynaptic depolarization. In addition to the well-described excitatory thalamostriatal projections, we identified a sparse population of GABAergic projection neurons in higher-order MGB that inhibit TS MSNs through a GABA<sub>B</sub>-receptor-mediated mechanism. Together, these results provide a conceptual framework for MGB-driven state-dependent modulation of striatal output signals.

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Publication Details

Journal
iScience
Published
2025-10-28
DOI
https://doi.org/10.1016/j.isci.2025.113880
Primary Topic
Neurological disorders and treatments
Type
article
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article

Inhibitory inputs from thalamus promote resilient spiking in tail of striatum

Jan Gründemann, Laura M. Haetzel
iScience
Neurological disorders and treatments
article

Inhibitory inputs from thalamus promote resilient spiking in tail of striatum

Jan Gründemann, Laura M. Haetzel
article en

Abstract

Thalamic afferents form glutamatergic synapses with striatal medium spiny neurons (MSNs). These projections are involved in complex learning processes and have primarily been studied in rostral striatum. Caudal regions, such as tail of striatum (TS), have only recently gained attention. Medial geniculate body (auditory thalamus; MGB) provides functional excitatory inputs to MSNs in TS; however, it is unclear how MGB regulates striatal output signals. We therefore performed optogenetics-assisted circuit mapping in <i>ex vivo</i> brain slices to examine how MGB modulates neuronal output in TS MSNs. Whole-cell recordings revealed that activation of MGB terminals increases MSN firing specifically at high levels of postsynaptic depolarization. In addition to the well-described excitatory thalamostriatal projections, we identified a sparse population of GABAergic projection neurons in higher-order MGB that inhibit TS MSNs through a GABA<sub>B</sub>-receptor-mediated mechanism. Together, these results provide a conceptual framework for MGB-driven state-dependent modulation of striatal output signals.

iScienceVol. 28(11)
German Center for Neurodegenerative Diseases (DE)
Openalex Percentile: Top 56%
Neurological disorders and treatments
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