Hippocampus–Prefrontal Coupling Regulates Recognition Memory for Novelty Discrimination

• DOI: 10.1523/jneurosci.1202-21.2021
• Publication Date: 2021-10-12T21:07:51Z
• Authors: Cong Wang; Teri M. Furlong; Peter G. Stratton; Conrad C. Y. Lee; Li Xu; Sam Merlin; Chris Nolan; Ehsan Arabzadeh; Roger Marek; Pankaj Sah
• Keywords: Male; 0301 basic medicine; 570; hippocampus; 1.2 Psychological and socioeconomic processes; 1.1 Normal biological development and functioning; 150; Prefrontal Cortex; 32 Biomedical and Clinical Sciences; Prefrontal cortex; Basic Behavioral and Social Science; Hippocampus; context; novelty; memory; Discrimination Learning; Rats, Sprague-Dawley; 03 medical and health sciences; anzsrc-for: 32 Biomedical and Clinical Sciences; Memory; Behavioral and Social Science; Neural Pathways; Psychology; Animals; anzsrc-for: 17 Psychology and Cognitive Sciences; 280102 - Expanding knowledge in the biological sciences; Neurons; prefrontal cortex; 0303 health sciences; 320903 - Central nervous system; Context; Neurosciences; Novelty; Recognition, Psychology; 004; Brain Disorders; Rats; Recognition; Mental Health; anzsrc-for: 11 Medical and Health Sciences; 3209 Neurosciences; Neurological; anzsrc-for: 3209 Neurosciences; Sprague-Dawley; recognition

Recognition memory provides the ability to distinguish familiar from novel objects and places, and is important for recording and updating events to guide appropriate behavior. The hippocampus (HPC) and medial prefrontal cortex (mPFC) have both been implicated in recognition memory, but the nature of HPC–mPFC interactions, and its impact on local circuits in mediating this process is not known. Here we show that novelty discrimination is accompanied with higher theta activity (4–10 Hz) and increased c-Fos expression in both these regions. Moreover, theta oscillations were highly coupled between the HPC and mPFC during recognition memory retrieval for novelty discrimination, with the HPC leading the mPFC, but not during initial learning. Principal neurons and interneurons in the mPFC responded more strongly during recognition memory retrieval compared with learning. Optogenetic silencing of HPC input to the mPFC disrupted coupled theta activity between these two structures, as well as the animals' (male Sprague Dawley rats) ability to differentiate novel from familiar objects. These results reveal a key role of monosynaptic connections between the HPC and mPFC in novelty discrimination via theta coupling and identify neural populations that underlie this recognition memory-guided behavior.SIGNIFICANCE STATEMENTMany memory processes are highly dependent on the interregional communication between the HPC and mPFC via neural oscillations. However, how these two brain regions coordinate their oscillatory activity to engage local neural populations to mediate recognition memory for novelty discrimination is poorly understood. This study revealed that the HPC and mPFC theta oscillations and their temporal coupling is correlated with recognition memory-guided behavior. During novel object recognition, the HPC drives mPFC interneurons to effectively reduce the activity of principal neurons. This study provides the first evidence for the requirement of the HPC–mPFC pathway to mediate recognition memory for novelty discrimination and describes a mechanism for how this memory is regulated.