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

Until recently, it was believed that hippocampal development was the primary rate-limiting factor in the developmental emergence of hippocampal forms of learning, such as trace eyeblink conditioning (EBC). Indeed, hippocampal neuronal activity shows an age-related increase in both complexity and task responsiveness during trace EBC. However, recent work from our laboratory suggests that sensory system development may also play a role. Training with the earlier-developing somatosensory system results in an earlier emergence of trace EBC in rats, suggesting that the development of sensory input to the hippocampus may influence the development of trace EBC. The goal of the current study was to examine the activity of hippocampal CA1 pyramidal cells during acquisition of trace EBC with an early-developing somatosensory CS. Rat pups were trained with a vibration CS on postnatal days (P) 17-19, P21-23, and P24-26 while CA1 pyramidal cell activity was recorded. Results indicated that CA1 neurons show an age-related increase in responsiveness to trial events. Although the magnitude of neuronal responding showed age-related increases in activity, all three age groups demonstrated learning-related increases in firing rate magnitude and peaks in firing rate were evident both at CS onset and offset. These findings suggest that the ontogeny of trace eyeblink conditioning is related to both hippocampal and sensory system development.

Sensory system development influences the ontogeny of trace eyeblink conditioning.

The developmental emergence of delay eyeblink conditioning (EBC) is dependent on the development of the sensory system stimulated by the conditioned stimulus (CS). However, trace EBC has traditionally been believed to be dependent on the development of forebrain structures, such as the hippocampus. If hippocampal development alone is limiting the developmental emergence of trace EBC, then using an earlier developing sensory modality should not affect the rate or asymptote of conditioning. The goal of the current study was to investigate whether using a vibration CS would facilitate the ontogeny of trace EBC relative to an auditory CS. Rat pups received six sessions of trace EBC or unpaired training using either a tone or vibration CS on postnatal day (P) 17-18, 21-22, or 24-25. Training with a vibration CS resulted in rapid conditioning as early as P17-18, whereas training with a tone CS did not result in rapid conditioning until after P17-18. The results suggest that the ontogeny of trace EBC depends, at least in part, on sensory system development.

Developmental Changes in Hippocampal CA1 Single Neuron Firing and Theta Activity during Associative Learning.

Hippocampal development is thought to play a crucial role in the emergence of many forms of learning and memory, but ontogenetic changes in hippocampal activity during learning have not been examined thoroughly. We examined the ontogeny of hippocampal function by recording theta and single neuron activity from the dorsal hippocampal CA1 area while rat pups were trained in associative learning. Three different age groups [postnatal days (P)17-19, P21-23, and P24-26] were trained over six sessions using a tone conditioned stimulus (CS) and a periorbital stimulation unconditioned stimulus (US). Learning increased as a function of age, with the P21-23 and P24-26 groups learning faster than the P17-19 group. Age- and learning-related changes in both theta and single neuron activity were observed. CA1 pyramidal cells in the older age groups showed greater task-related activity than the P17-19 group during CS-US paired sessions. The proportion of trials with a significant theta (4-10 Hz) power change, the theta/delta ratio, and theta peak frequency also increased in an age-dependent manner. Finally, spike/theta phase-locking during the CS showed an age-related increase. The findings indicate substantial developmental changes in dorsal hippocampal function that may play a role in the ontogeny of learning and memory.

Developmental changes in hippocampal associative coding.

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 eyeblink conditioning.

A rate-limiting factor in the ontogeny of auditory eyeblink conditioning (EBC) is the development of sensory inputs to the pontine nucleus. One possible way to facilitate the emergence of EBC would be to use a conditioned stimulus (CS) that activates an earlier-developing sensory system. The goal of the current study was to investigate whether using a vibration CS would facilitate the ontogeny of delay EBC relative to an auditory CS. Rat pups received six sessions of delay EBC or unpaired training using either a tone or vibration CS on postnatal day (P)14-15, 17-18, 21-22, or 24-25. Conditioning with a vibration CS resulted in rapid learning as early as P17-18, whereas conditioning with a tone CS did not result in rapid conditioning until after P17-18. Control experiments verified that the differences in EBC were due to CS-specific sensory properties. The results suggest that the ontogeny of EBC depends on sensory system development.