Delay-related activity in marmoset prefrontal cortex

Abstract

Persistent delay-period activity in prefrontal cortex (PFC) has long been regarded as a neural signature of working memory (WM). Electrophysiological investigations in macaque PFC have provided much insight into WM mechanisms; however, a barrier to understanding is the fact that a portion of PFC lies buried within the principal sulcus in this species and is inaccessible for laminar electrophysiology or optical imaging. The relatively lissencephalic cortex of the New World common marmoset (Callithrix jacchus) circumvents such limitations. It remains unknown, however, whether marmoset PFC neurons exhibit persistent activity. Here, we addressed this gap by conducting wireless electrophysiological recordings in PFC of marmosets performing a delayed-match-to-location task on a home cage-based touchscreen system. As in macaques, marmoset PFC neurons exhibited sample-, delay-, and response-related activity that was directionally tuned and linked to correct task performance. Models constructed from population activity consistently and accurately predicted stimulus location throughout the delay period, supporting a framework of delay activity in which mnemonic representations are relatively stable in time. Taken together, our findings support the existence of common neural mechanisms underlying WM performance in PFC of macaques and marmosets and thus validate the marmoset as a suitable model animal for investigating the microcircuitry underlying WM.

Functional Specialization and Distributed Processing across Marmoset Lateral Prefrontal Subregions

“…Upon observing single- or multiunit activity at multiple sites of the array for approximately three weeks, we commenced unrestrained datalogger recordings of extracellular activity from the 96 implanted electrodes. A detailed description of these unrestrained datalogger-based recordings is presented in Wong et al (2023). Initially, neural data underwent processing with a common median filter to mitigate large movement-related artifacts.…”

“…Previously published data from Wong and colleagues (2023) was included here. Activity within distinct non-overlapping task epochs was assessed using analyses of variance (ANOVA) to compare the mean discharge rates of each neuron for each condition (four spatial locations) and each task epoch (baseline, sample, delay, pre-response and post-response).…”

“…Marmosets were euthanized at the end of the data acquisition process to prepare the brains for ex-vivo MRI scans (Wong et al 2023). The animals were deeply anesthetized with 20 mg/kg of ketamine plus 0.025 mg/kg medetomidine and 5% isoflurane in 1.4-2% oxygen to reach beyond the surgical plane (i.e., no response to toe pinching or cornea touching).…”

“…Consequently, considerable effort has been directed toward an understanding of the cytoarchitectural differentiation of PFC subregions, and indeed the marmoset lPFC is comprised of a number of cytoarchitecturally distinct subfields believed to be homologous with those of macaques and humans (Burman et al 2006; Reser et al 2013). Owing to the relatively recent surge in popularity of the marmoset model however (Mitchell and Leopold 2015; Okano 2021), the functions associated with these subregions are relatively poorly understood in this species and are an area of intensive investigation (Blum et al 1982; Hung et al 2015; Johnston et al 2019; Liu et al 2019; Schaeffer, Gilbert, Gati, et al 2019; Schaeffer, Gilbert, Hori, et al 2019; Selvanayagam et al 2019; Schaeffer et al 2020; Feizpour et al 2021; Jovanovic et al 2022; Wong et al 2023). Given the well-established link between the lPFC and cognition, and the unique potential of the marmoset model for deriving an understanding of the cortical microcircuitry underlying aspects of social cognition such as vocal communication (Miller et al 2016; Jovanovic et al 2022; Samandra et al 2022; Grijseels et al 2023), establishing a correspondence between the structural and functional organization of lPFC with respect to relatively simple tasks and social stimuli of multiple modalities is needed to provide an empirical foundation for interpretation of these more complex processes.…”

The neurobiology of vocal communication in marmosets

“…Because of the marmosets relatively small body size, wireless equipment must be lightweight to not impede the animals' movements, 193 while at the same time, it must be designed to withstand the rigors of a 3D arboreal lifestyle. Recent studies using wireless recordings in marmosets have shown promising results, 193,195 recordings from up to 96 channels simultaneously while the marmoset is freely moving in the home cage. Employing such wireless recording technologies and combining them with wearable microphones and behavior tracking opens the door to a range of new questions related to marmoset vocal communication that were not possible even just a few years ago.…”