Developmental Changes in Hippocampal Associative Coding

Abstract

Behavioral analyses of the ontogeny of memory have shown that hippocampus-dependent learning emerges relatively late in postnatal development compared with simple associative learning. Maturation of hippocampal mnemonic mechanisms has been hypothesized to underlie the development of the later emerging learning processes. However, the role of hippocampal maturation in learning has not been examined directly. The goal of the present study was to examine developmental changes in hippocampal neuronal coding during acquisition of a hippocampus-dependent learning task. We recorded activity from CA1 pyramidal cells in rat pups while they were trained on trace eyeblink conditioning. Trace eyeblink conditioning is a Pavlovian conditioning task that involves the association of a conditioned stimulus (CS) with an unconditioned stimulus over a stimulus-free trace interval. The inclusion of the trace interval is what makes the task hippocampus dependent. In the present study, rats were trained at 21-23, 24 -26, and 31-33 d of age. Previous research from our laboratory and others shows that trace conditioning begins to emerge during the third postnatal week. The results indicate that hippocampal neurons show a substantial increase in responsiveness to task-relevant events during development. Moreover, there is an age-related increase in the proportion of neurons that respond to a combination of trial events (e.g., CS and trace). Our findings indicate that the developmental emergence of hippocampally mediated learning is related to increases in the strength and complexity of CA1 associative coding.

Sensory system development influences the ontogeny of hippocampal associative coding and trace eyeblink conditioning

“…As previously described (Goldsberry et al, 2015), microdrive implantation involved drilling a small hole in the skull directly above the right dorsal hippocampus (AP, −4.0 mm; ML, −2.5 mm). The base of microdrive was lowered through the hole until the tetrodes touched the brain surface.…”

“…These clusters were then manually inspected and refined using MClust-3.5 (Redish et al, 2010). Neurons were classified as pyramidal cells if they (1) showed a bursting pattern of activity as demonstrated by a peak in the autocorrelogram at 3–8 ms, (2) had a baseline (500 ms sample duration prior to CS onset) firing rate of less than 10.5 spikes/second, and (3) had at least 100 spikes during the training session (Goldsberry et al 2015). …”

“…First, neurons were categorized according to their firing rate profile (responsive to CS, trace interval, US, or a combination thereof) (Goldsberry et al, 2015). To accomplish this, each trial was divided into nine 125 ms intervals.…”

“…Most importantly, work from our laboratory has shown that hippocampal neuronal activity is correlated with the developmental emergence of trace EBC (Goldsberry, Kim, & Freeman, 2015). We recorded CA1 pyramidal cell activity while rat pups were trained in auditory trace eyeblink conditioning.…”

“…The goal of the current study was to elucidate the role of CS modality on the ontogeny of hippocampal neuronal activity during trace eyeblink conditioning. If sensory input to the hippocampus is not playing a role in the development of trace EBC, then pups trained in somatosensory trace eyeblink conditioning should show identical levels of neuronal responsiveness to those trained in auditory trace conditioning (Goldsberry et al, 2015). However, if the development of sensory input to the hippocampus is limiting the ontogenetic emergence of trace EBC, then we would anticipate that training pups with an earlier-developing sensory modality would result in increased hippocampal neuronal responsiveness to trial stimuli.…”