Differential responsivity of neurons in perirhinal cortex, lateral entorhinal cortex, and dentate gyrus during time‐bridging learning

Abstract

Many studies have focused on the function of hippocampal region CA1 as a critical site for associative memory, but much less is known about changes in the afferents to CA1. Here we report the activity of multiple single neurons from perirhinal and entorhinal cortex and from dentate gyrus during trace eyeblink conditioning as well as consolidated recall, and in pseudo‐conditioned control rabbits. We also report an analysis of theta activity filtered from the local field potential (LFP). Our results show early associative changes in single‐neuron firing rate as well as theta oscillations in lateral entorhinal cortex (EC) and dentate gyrus (DG), and increases in the number of responsive neurons in perirhinal cortex. In both EC and DG, a subset of neurons from conditioned animals exhibited an elevated baseline firing rate and large responses to the conditioned stimulus and trace period. A similar population of cells has been seen in DG and in medial, but not lateral, EC during spatial tasks, suggesting that lateral EC contains cells responsive to a temporal associative task. In contrast to recent studies in our laboratory that found significant CA1 contributions to long‐term memory, the activity profiles of neurons within EC and DG were similar for conditioned and pseudoconditioned rabbits during post‐consolidation sessions. Collectively these results demonstrate that individual subregions of medial temporal lobe differentially support new and remotely acquired memories. Neuron firing profiles were similar on training trials when conditioned responses were and were not exhibited, demonstrating that these temporal lobe regions represent the CS–US association and do not control the behavioral response. The analysis of theta activity revealed that theta power was modulated by the conditioning stimuli in both the conditioned and pseudoconditioned groups and that although both groups exhibited a resetting of phase to the corneal airpuff, only the conditioned group exhibited a resetting of phase to the whisker conditioned stimulus.

Preferential frequency‐dependent induction of synaptic depression by the lateral perforant path and of synaptic potentiation by the medial perforant path inputs to the dentate gyrus

“…Intrinsic firing activity in the LEC is very low (>1 Hz) and under trace learning conditions can increase to over 3 Hz (Suter et al, 2019). In anesthetized rats, resting activity in the range of 2–8 Hz has been detected in the DG (Dickson et al, 1994; Gloveli et al, 1997).…”

Effects of neonatal isoflurane anesthesia exposure on learning-specific and sensory systems in adults

“…Together, these results indicate that neonatal exposure to general anesthesia induces chronic changes to hippocampal microstructure which could contribute to the learning deficiency that was measured at the stage of adolescence. CA1 is considered to be a critical site for associative memory and neurons in DG participate in the processing of learning-related information 45 . It has been shown previously that miR-132, one of the microRNAs responsible for positive regulation of dendritic spines was downregulated at different time points (P14, P28, P60) after neonatal rats were exposed to propofol 46 .…”

Genetic Ablation of Neural Progenitor Cells Impairs Acquisition of Trace Eyeblink Conditioning

“…Recent work by Suter et al (2019) discovered cells within dentate gyrus that showed changes in the firing rate that started at CS onset and persisted through the trace period during tEBC. This finding suggests that there are cells within DG that are bridging the temporal gap between stimuli, which would play a vital role in associative learning.…”

“…Neurogenesis in the adult brain occurs in the dentate gyrus (DG) and produces new neurons that mature into granule cells and integrate into existing circuitry (Altman and Das, 1965; Dayer et al, 2003). These highly excitable neural progenitor cells are believed to play a role in memory formation by providing enhanced plasticity to the hippocampus (Snyder et al, 2001; Mongiat et al, 2009; Suter et al, 2019). Indeed, there are some studies that have found that reducing the number of newborn neurons impairs memory acquisition on different associative memory tasks.…”