Reconfiguration of prefrontal-striatal-hippocampal networks during rule-based category learning in rats

Categorization depends on multiple brain regions, including the prefrontal cortex, striatum, and hippocampus. However, it remains unclear how these regions interact during category learning. We recorded activity in the medial prefrontal cortex (mPFC), dorsomedial striatum (DMS), and the dorsal hippocampus (dHPC) as rats (n = 9, 3 females) learned a rule-based categorization task.

Category-selectivity emerged early in the mPFC. In the DMS and dHPC, category-selectivity increased after learning and peaked before the rats’ decisions. A linear regression analysis revealed that all regions contained neurons with stimulus-related selectivity, decision-related selectivity, and “mixed selectivity”.

From the local field potentials (LFPs), Granger causality revealed a learning-related reconfiguration of network synchrony. DMS-mPFC theta (4-10 Hz) causality was strongest during early training sessions and was directional from the DMS to the mPFC. mPFC-dHPC theta causality peaked during middle training sessions and was directional from the mPFC to dHPC. dHPC-DMS theta causality increased across training and was directional from the dHPC to the DMS. mPFC-dHPC causality and DMS-dHPC causality peaked before the rats’ decisions. The results indicate that early training sessions engaged a frontal-striatal circuit, whereas later training sessions engaged a hippocampal-striatal circuit.

The transition to a hippocampal-striatal circuit is potentially mediated by top-down mPFC control. J.H.F. discloses support for the research of this work from the National Institutes of Health Grant P01-HD080679. J.K discloses support for publication of this work from National Research Foundation of Korea NRF-2024S1A5A8019683.

M.B.B, S.J.F, and H.E.H declare no relevant funding. These authors contributed equally: Matthew B. Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Matthew B.

Broschard, Jangjin Kim, Hunter E. Freeman The Picower Institute of Learning and Memory, MIT, Cambridge, MA, USA Department of Psychology, Kyungpook National University, Daegu, Korea The authors declare no competing interests. Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.