Hippocampal and cerebellar single-unit activity during delay and trace eyeblink conditioning in the rat

Abstract

In delay eyeblink conditioning, the CS overlaps with the US and only a brainstem-cerebellar circuit is necessary for learning. In trace eyeblink conditioning, the CS ends before the US is delivered and several forebrain structures, including the hippocampus, are required for learning, in addition to a brainstem-cerebellar circuit. The interstimulus interval (ISI) between CS onset and US onset is perhaps the most important factor in classical conditioning, but studies comparing delay and trace conditioning have typically not matched these procedures in this crucial factor, so it is often difficult to determine whether results are due to differences between delay and trace or to differences in ISI.In the current study, we employed a 580-ms CS-US interval for both delay and trace conditioning and compared hippocampal CA1 activity and cerebellar interpositus nucleus activity in order to determine whether a unique signature of trace conditioning exists in patterns of single-unit activity in either structure. Long-Evans rats were chronically implanted in either CA1 or interpositus with microwire electrodes and underwent either delay eyeblink conditioning, or trace eyeblink conditioning with a 300-ms trace period between CS offset and US onset. On trials with a CR in delay conditioning, CA1 pyramidal cells showed increases in activation (relative to a pre-CS baseline) during the CS-US period in sessions 1-4 that was attenuated by sessions 5-6. In contrast, on trials with a CR in trace conditioning, CA1 pyramidal cells did not show increases in activation during the CS-US period until sessions 5-6. In sessions 5-6, increases in activation were present only to the CS and not during the trace period. For rats with interpositus electrodes, activation of interpositus neurons on CR trials was present in all sessions in both delay and trace conditioning. However, activation was greater in trace compared to delay conditioning in the first half of the CS-US interval (during the trace CS) during early sessions of conditioning and, in later sessions of conditioning, activation was greater in the second half of the CS-US interval (during the trace interval). These results suggest that the pattern of hippocampal activation that differentiates trace from delay eyeblink conditioning is a slow buildup of activation to the CS, possibly representing encoding of CS duration or discrimination of the CS from the background context. Interpositus nucleus neurons show strong modeling of the eyeblink CR regardless of paradigm but show a changing pattern across conditioning that may be due to the necessary contributions of forebrain processing to trace conditioning.

Classical eyeblink conditioning using electrical stimulation of caudal mPFC as conditioned stimulus is dependent on cerebellar interpositus nucleus in guinea pigs

“…It is consistent with the findings of the previous studies using peripheral CS in eyeblink conditioning that cerebellar interpositus nucleus plays an essential role in CR expression [4,27,29,31,66,70,71] . Steinmetz [72] speculated that the cerebellum may only be involved in simple, discrete, aversive, and somatic associative learning that occurs with a relatively short interstimulus interval.…”

Parallel acquisition of awareness and differential delay eyeblink conditioning

“…Studies of firing rates in hippocampal pyramidal cells have shown learning-related neural plasticity over the course of delay eyeblink conditioning, which are strongly predictive of the subsequent emergence of CRs Green and Arenos 2007). Neuroimaging studies in humans show similar learning-related activity in the hippocampus during delay eyeblink conditioning (Blaxton et al 1996).…”

Developmental Changes in Hippocampal Associative Coding

“…Several approaches have been used to examine the development of learning, including behavioral analyses of hippocampus-dependent tasks such as spatial learning. Spatial learning emerges relatively late in altricial species and parallels some aspects of hippocampal anatomical development (Rudy and Paylor, 1988;Green and Stanton, 1989;Freeman and Stanton, 1991). Rudy and Paylor (1988) found that although postnatal day 22 (P22) rat pups successfully learn the water maze place-learning task, P19 pups are unable to.…”