Thalamic and prefrontal cortical inputs engage cholinergic interneurons in the nucleus accumbens core in sharply different ways, according to a study of the circuit. The thalamic pathway showed strong facilitation, while the cortical pathway showed marked depression.
The work asks how cortical and thalamic connections reach these cells and how those inputs affect their responses. The authors frame the findings as showing how nucleus-accumbens-core cholinergic interneurons process long-range inputs and as highlighting differences from equivalent circuits elsewhere in the striatum. That gives the report a focused question: not just where the inputs come from, but how the target cells handle them.
Tracing the incoming routes
To map the incoming routes, the researchers used cell-type-specific retrograde anatomy, a tracing method for identifying putative afferents. In other words, the analysis worked backward from the target cell type to locate possible sources of its input. It identified the prefrontal cortex and thalamus as putative afferents to the target interneurons.
They then combined ex vivo slice physiology with optogenetics to characterize synapses onto the interneurons. The first approach uses brain slices outside the living animal, while the second uses light to engage selected inputs. Together, the methods linked the source of an input with the way the target cells responded.
The study's physiological question was therefore more specific than whether a connection existed. It asked how cortical and thalamic inputs behaved when their signals reached the cholinergic interneurons, bringing connectivity and functional impact into the same analysis.
A contrast in the cell responses
Those tests produced a marked contrast. Thalamic inputs showed strong facilitation, while cortical inputs showed marked depression. In plain terms, the two long-range sources did not produce the same response pattern in the target cells under the reported experimental conditions.
Both AMPA and NMDA receptors contributed to responses from the cortical and thalamic inputs. The report therefore does not assign the contrast to one receptor class alone; it describes contributions from both receptor systems across both pathways. The functional analysis also included action-potential generation and spontaneous firing, extending the work from synaptic responses to the cells' electrical activity.
How to read the finding
The authors interpret this pattern as evidence about how nucleus-accumbens-core cholinergic interneurons process long-range inputs. They also present it as highlighting differences from equivalent circuits elsewhere in the striatum. At the level directly described, the study identifies putative inputs and characterizes their synaptic and firing effects.
The document supplied for review labels the work a preprint that has not yet been peer reviewed by a journal. That is important context because the reported results are qualitative: the account describes strong facilitation, marked depression and receptor contributions rather than giving numerical effect estimates in the material provided.
Full text is stated to be available from the preprint server, while the selected license terms do not permit archiving in PMC. The supplied text does not identify a study-specific funder; its funding-related wording is a generic note about NIH-funded preprints.
Paper data and sources
Original title: Differential Cortical and Thalamic Engagement of Cholinergic Interneurons in the Nucleus Accumbens Core.
Authors: Emily V Jang, Nigel Dao, Lilly Cole, Adam G Carter
Journal/Repository: The Journal of neuroscience : the official journal of the Society for Neuroscience
Status: Peer-reviewed
First online: 2026-09-30
DOI: 10.1523/jneurosci.1919-25.2026
Original paper