Striatal interneuron microcircuits gate reinforcement to stabilize adaptive choice

Abstract

The dorsomedial striatum guides learning and adaptive decision-making through excitatory synaptic control of its spiny projection neuron outputs. However, the contributions of local inhibitory microcircuitry remain poorly understood. Here, we identify an interneuron circuit in the dorsomedial striatum that links outcome processing to adaptive action selection. During probabilistic push-pull reversal learning, interneurons represented immediate outcomes: somatostatin interneurons were recruited on unrewarded trials and unexpected rewarded trials, whereas tyrosine hydroxylase interneurons were suppressed on unrewarded trials and recruited on rewarded trials. In vivo recruitment of tyrosine hydroxylase interneurons suppressed somatostatin interneuron activity and increased activity in both direct- and indirect-pathway striatal projection neurons, revealing a polysynaptic disinhibitory microcircuit. Transient inhibition of somatostatin interneurons in this pull-tuned region produced a sustained increase in aberrant pull choices and occupancy of a suboptimal pull-preferring behavioral state, whereas inhibition of tyrosine hydroxylase interneurons produced a sustained impairment of pull reinforcement. Longer-term policy changes following somatostatin interneuron inhibition coincided with postsynaptic potentiation of excitatory synapses onto striatal projection neurons, suggesting a potential substrate for the persistence of altered behavioral policies. Together, these findings identify a disinhibitory striatal circuit motif gating reinforcement which transforms individual trial outcomes into temporally broader policy.

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BibTeX RIS

BibTeX

@misc{iliakis2026striatal,
  title = {{Striatal interneuron microcircuits gate reinforcement to stabilize adaptive choice}},
  author = {E. A. Iliakis and J. M. Muhsinov and A. N. Ramirez and F. G. Rinaldi and J. Galanaugh and S. Pandey and C. I. Linares-Garcia and A. R. Tachau and E. Z. Song and L. Vargas and K. Choi and J. T. Woolley and S. M. Ferrigno and E. A. Diaz-Hernandez and E. N. Holly and D. J. Margolis and E. Piasini and M. V. Fuccillo},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.21.753300},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753300v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Striatal interneuron microcircuits gate reinforcement to stabilize adaptive choice
AU  - E. A. Iliakis
AU  - J. M. Muhsinov
AU  - A. N. Ramirez
AU  - F. G. Rinaldi
AU  - J. Galanaugh
AU  - S. Pandey
AU  - C. I. Linares-Garcia
AU  - A. R. Tachau
AU  - E. Z. Song
AU  - L. Vargas
AU  - K. Choi
AU  - J. T. Woolley
AU  - S. M. Ferrigno
AU  - E. A. Diaz-Hernandez
AU  - E. N. Holly
AU  - D. J. Margolis
AU  - E. Piasini
AU  - M. V. Fuccillo
PY  - 2026
DA  - 2026/09/21
PB  - bioRxiv
DO  - 10.64898/2026.09.21.753300
UR  - https://www.biorxiv.org/content/10.64898/2026.09.21.753300v1
AB  - The dorsomedial striatum guides learning and adaptive decision-making through excitatory synaptic control of its spiny projection neuron outputs. However, the contributions of local inhibitory microcircuitry remain poorly understood. Here, we identify an interneuron circuit in the dorsomedial striatum that links outcome processing to adaptive action selection. During probabilistic push-pull reversal learning, interneurons represented immediate outcomes: somatostatin interneurons were recruited on unrewarded trials and unexpected rewarded trials, whereas tyrosine hydroxylase interneurons were suppressed on unrewarded trials and recruited on rewarded trials. In vivo recruitment of tyrosine hydroxylase interneurons suppressed somatostatin interneuron activity and increased activity in both direct- and indirect-pathway striatal projection neurons, revealing a polysynaptic disinhibitory microcircuit. Transient inhibition of somatostatin interneurons in this pull-tuned region produced a sustained increase in aberrant pull choices and occupancy of a suboptimal pull-preferring behavioral state, whereas inhibition of tyrosine hydroxylase interneurons produced a sustained impairment of pull reinforcement. Longer-term policy changes following somatostatin interneuron inhibition coincided with postsynaptic potentiation of excitatory synapses onto striatal projection neurons, suggesting a potential substrate for the persistence of altered behavioral policies. Together, these findings identify a disinhibitory striatal circuit motif gating reinforcement which transforms individual trial outcomes into temporally broader policy.
ER  -

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