Learning differentially shapes prefrontal and hippocampal activity during classical conditioning

Abstract

The ability to use sensory cues to inform goal directed actions is a critical component of behavior. To study how sounds guide anticipatory licking during classical conditioning, we employed high-density electrophysiological recordings from the hippocampal CA1 area and the prefrontal cortex (PFC) in mice. CA1 and PFC neurons undergo distinct learning dependent changes at the single cell level and maintain representations of cue identity at the population level. In addition, reactivation of task-related neuronal assemblies during hippocampal awake Sharp-Wave Ripples (aSWR) changed within individual sessions in CA1 and over the course of multiple sessions in PFC. Despite both areas being highly engaged and synchronized during the task, we found no evidence for coordinated single cell or assembly activity during conditioning trials or aSWR. Taken together, our findings support the notion that persistent firing and reactivation of task-related neural activity patterns in CA1 and PFC support learning during classical conditioning.

Emergence of persistent and sequential representations in the hippocampal-prefrontal circuitry during associative learning

“…Figure S5G). It seems that the presence of coordinated activity between those two areas may vary according to the type and period of the task (e.g., sleep, sharp-wave ripples, sensory encoding), which would explain previous work showing both dependent Jadhav et al (2016), Peyrache et al (2009), Shin et al (2019) and independent (Kaefer et al (2020), Klee et al (2021)) co-activation of neuronal patterns in those areas. In our case, any relevant interplay between those two areas during the late stimulus or trace period could not be captured by HMM states.…”

“…We previously developed an appetitive trace conditioning task (Klee et al, 2021) which trained mice to differentiate between two sound stimuli (conditioned stimulus: CS+ and CS-;Figure 1A). In each CS+ trial, the 2s stimulus was followed by a 1s delay (trace period), and a reward delivered in a water port.…”

“…In this work, we aimed at elucidating the neural mechanisms leading to the emergence of a temporal association, linking events occurring at different times. To this end, we recorded neurons from the hippocampal area CA1 and mPFC of mice engaged in an appetitive auditory trace-conditioning task (Klee et al (2021)), and examined how learning shaped the relationship between stimulus responses, temporal encoding, and behavior. We found that both conditioned (CS) and unconditioned stimuli (US) triggered the onset of temporal sequences in both CA1 and mPFC, which in turn were differentially modulated by learning.…”

The hearing hippocampus

“…Training animals to associate a particular sound (conditioned stimulus) with a subsequent reward or punishment (unconditioned stimulus) elicits changes in hippocampal activity over the course of learning (see Supplementary Table D). Different hippocampal synapses are modified in strength through long term potentiation (for a review see Gruart et al, 2015), leading to changes in firing rates that come to differentiate sounds that have been associated with value from those that have not (Berger et al, 1976;Disterhoft and Segal, 1978;Klee et al, 2021;Olds and Hirano, 1969). Such differential responses can arise between tones of different frequencies, or between more complex sounds such as artificial vowels with different formant structure (Itskov et al, 2012).…”

Combining Cortical Voltage Imaging and Hippocampal Electrophysiology for Investigating Global, Multi-Timescale Activity Interactions in the Brain

“…Hippocampal–cortical interactions have been widely studied with the aim of understanding their role in supporting memory [ 1 , 2 , 3 , 4 ]. Yet, most studies have focused on the interplay between the hippocampus and selected cortical areas with major anatomical connections to the hippocampus, such as the entorhinal or the medial prefrontal cortex [ 4 , 5 , 6 , 7 ]. Less is known about the interrelation between hippocampal activity and activity phenomena spanning large portions of cortical space [ 8 , 9 , 10 ].…”