Learning‐related changes in cellular activity within mouse dentate gyrus during trace eyeblink conditioning

Abstract

Because the dentate gyrus serves as the first site for information processing in the hippocampal trisynaptic circuit, it an important structure for the formation of associative memories. Previous findings in rabbit had recorded populations of cells within dentate gyrus that may bridge the temporal gap between stimuli to support memory formation during trace eyeblink conditioning, an associative learning task. However, this previous work was unable to identify the types of cells demonstrating this type of activity. To explore these changes further, we did in vivo single‐neuron recording in conjunction with physiological determination of cell types to investigate the functional role of granule cells, mossy cells, and interneurons in dentate gyrus during learning. Tetrode recordings were performed in young‐adult mice during training on trace eyeblink conditioning, a hippocampal‐dependent temporal associative memory task. Conditioned mice were able to successfully learn the task, with male mice learning at a faster rate than female mice. In the conditioned group, granule cells tended to show an increase in firing rate during conditioned stimulus presentation while mossy cells showed a decrease in firing rate during the trace interval and the unconditioned stimulus. Interestingly, populations of interneurons demonstrated learning‐related increases and decreases in activity that began at onset of the conditioned stimulus and persisted through the trace interval. The current study also found a significant increase in theta power during stimuli presentation in conditioned animals, and this change in theta decreased over time. Ultimately, these data suggest unique involvement of granule cells, mossy cells, and interneurons in dentate gyrus in the formation of a trace associative memory. This work expands our knowledge of dentate gyrus function, helping to discern how aging and disease might disrupt this process.

WITHDRAWN: Excitatory effects of dentate gyrus mossy cells on granule cells and area CA3: an vitro and in vivo study in adult mice

“…Mossy cells (MCs) of the dentate gyrus (DG) play an important role in many cognitive and behavioral functions of the DG, such as spatial memory, recognition of novelty in the environment, and regulating anxiety(Scharfman, 2016; Danielson et al, 2017; Nakazawa, 2017; Senzai and Buzsaki, 2017; Botterill et al, 2021b; Fredes and Shigemoto, 2021; Wang et al, 2021; GoodSmith et al, 2022; Miller et al, 2022; Kim et al, 2023). MCs also contribute to diseases where the DG is implicated, such as temporal lobe epilepsy (Sloviter, 1994; Blumcke et al, 2000; Ratzliff et al, 2002; Jinde et al, 2012; Scharfman, 2016; Bui et al, 2018; Botterill et al, 2019).…”

Time cells emerge early in learning and encode stimulus modality past task requirements

“…This phenomenon mirrors cellular-level observations from past research (Moyer Jr. et al, 1996), which noted an increase in CA1 pyramidal cell excitability post-learning acquisition, peaking 24 hours after and returning to baseline within seven days. Similarly, (Miller et al, 2022)documented enhanced granule cell excitability in the dentate gyrus, upstream of CA1, correlating with learning progression, suggesting a broader neural adaptability mechanism during learning phases.…”

The Role of Cerebellar Intrinsic Neuronal Excitability, Synaptic Plasticity, and Perineuronal Nets in Eyeblink Conditioning

“…Figure 1 shows an unpublished waterfall plot of responding in a freely moving adult rat given paired CS–US presentations. More recently, mouse eyeblink conditioning has been explored with several different recording techniques using head-fixed mice that walk on a movable surface, such as a ball or cylinder [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”