Reciprocal projections between the globus pallidus externa and cortex span motor and nonmotor regions

E Emily A. Ferenczi (HHMI, Department of Neurobiology, Harvard Medical School) W Wengang Wang A Anushka Biswas (HHMI, Department of Neurobiology, Harvard Medical School) T Trent Pottala (HHMI, Department of Neurobiology, Harvard Medical School) Y Yihuan Dong (HHMI, Department of Neurobiology, Harvard Medical School) A Alison K. Chan (HHMI, Department of Neurobiology, Harvard Medical School) M Madeline A. Albanese R Raina S. Sohur (HHMI, Department of Neurobiology, Harvard Medical School) T Tingying Jia (Princeton Neuroscience Institute, Princeton University) K Kevin J. Mastro (HHMI, Department of Neurobiology, Harvard Medical School) B Bernardo L. Sabatini

Abstract

The globus pallidus externa (GPe) is a heterogeneous nucleus of the basal ganglia, with intricate connections to other basal ganglia nuclei, as well as direct connections to the cortex. The anatomic, molecular, and electrophysiologic properties of cortex-projecting pallidocortical neurons are not well characterized. Here, we show that pallidocortical neurons project to diverse motor and nonmotor cortical regions, are organized topographically in the GPe, and segregate into at least two distinct electrophysiological and molecular phenotypes. In addition, we find that the GPe receives direct synaptic input from deep layers of diverse motor and nonmotor cortical regions, some of which form reciprocal connections onto pallidocortical neurons. These results demonstrate the existence of a fast, bidirectional circuit between the GPe and the cortex that is ideally positioned to integrate information about behavioral goals, internal states, and environmental cues to rapidly modulate behavior.

Article Details

Volume / Issue Vol. 122, Issue 23
Published June 10, 2025
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (11)

E

Emily A. Ferenczi

HHMI, Department of Neurobiology, Harvard Medical School

W

Wengang Wang

A

Anushka Biswas

HHMI, Department of Neurobiology, Harvard Medical School

T

Trent Pottala

HHMI, Department of Neurobiology, Harvard Medical School

Y

Yihuan Dong

HHMI, Department of Neurobiology, Harvard Medical School

A

Alison K. Chan

HHMI, Department of Neurobiology, Harvard Medical School

M

Madeline A. Albanese

R

Raina S. Sohur

HHMI, Department of Neurobiology, Harvard Medical School

T

Tingying Jia

Princeton Neuroscience Institute, Princeton University

K

Kevin J. Mastro

HHMI, Department of Neurobiology, Harvard Medical School

B

Bernardo L. Sabatini