Distinctive physiology of molecularly identified medium spiny neurons in the macaque putamen

Jonathan T Ting; Nelson J Johansen; Brian E Kalmbach; Naz Taskin; Brian Lee; Jason K Clark; Rennie Kendrick; Lindsay Ng; Cristina Radaelli; Natalie Weed; Rachel Enstrom; Shea Ransford; Ingrid Redford; Sarah Walling-Bell; Rachel Dalley; Michael Tieu; Jeff Goldy; Nik Jorstad; Kimberly Smith; Trygve Bakken; Ed S Lein; Scott F Owen

doi:10.1016/j.celrep.2024.114963

Distinctive physiology of molecularly identified medium spiny neurons in the macaque putamen

Cell Rep. 2024 Nov 7;43(11):114963. doi: 10.1016/j.celrep.2024.114963. Online ahead of print.

Authors

Jonathan T Ting¹, Nelson J Johansen², Brian E Kalmbach³, Naz Taskin², Brian Lee², Jason K Clark⁴, Rennie Kendrick⁴, Lindsay Ng², Cristina Radaelli², Natalie Weed², Rachel Enstrom², Shea Ransford², Ingrid Redford², Sarah Walling-Bell², Rachel Dalley², Michael Tieu², Jeff Goldy², Nik Jorstad², Kimberly Smith², Trygve Bakken², Ed S Lein⁵, Scott F Owen⁶

Affiliations

¹ Allen Institute for Brain Science, Seattle, WA 98109, USA; The Washington National Primate Research Center, University of Washington, Seattle, WA 98195, USA; Department of Neurobiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
² Allen Institute for Brain Science, Seattle, WA 98109, USA.
³ Allen Institute for Brain Science, Seattle, WA 98109, USA; Department of Neurobiology and Biophysics, University of Washington, Seattle, WA 98195, USA.
⁴ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁵ Allen Institute for Brain Science, Seattle, WA 98109, USA; Department of Neurological Surgery, University of Washington School of Medicine, Seattle, WA 98195, USA.
⁶ Allen Institute for Brain Science, Seattle, WA 98109, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: sfowen@stanford.edu.

PMID: 39514389
DOI: 10.1016/j.celrep.2024.114963

Abstract

The distinctive physiology of striatal medium spiny neurons (MSNs) underlies their ability to integrate sensory and motor input. In rodents, MSNs have a hyperpolarized resting potential and low input resistance. When activated, they have a delayed onset of spiking and regular spike rate. Here, we show that in the macaque putamen, latency to spike is reduced and spike rate adaptation is increased relative to mouse. We use whole-cell brain slice recordings and recover single-cell gene expression using Patch-seq to distinguish macaque MSN cell types. Species differences in the expression of ion channel genes including the calcium-activated chloride channel, ANO2, and an auxiliary subunit of the A-type potassium channel, DPP10, are correlated with species differences in spike rate adaptation and latency to the first spike, respectively. These surprising divergences in physiology better define the strengths and limitations of mouse models for understanding neuronal and circuit function in the primate basal ganglia.

Keywords: CP: Cell biology; CP: Neuroscience; Patch-Seq; cross-species divergence; latency to spike; macaque; medium spiny neurons; mouse; physiology; putamen; single-cell gene expression; spike rate adaptation; spike rates; striatum.