Ontogeny of trace eyeblink conditioning to shock-shock pairings in the rat pup.

Rats are responsive to shock from an early age, but eyeblink conditioning to a tone-conditioned stimulus (conditional stimulus; CS) paired with a shock-unconditioned stimulus (US) does not emerge until postnatal Day 20 (P20). More generalized postural responses such as conditioned freezing can occur at P16. Using the same periorbital shock as both the CS and US in a US-US conditioning paradigm previously shown to be effective in adult animals, we found that shock-shock pairings with a 200-ms trace interval resulted in eyeblink conditioning in younger animals than previously thought. Some rat pups showed conditioned eyeblink responses as early as P12, and by P18, conditioned responses were fully developed in all animals. Unpaired control subjects confirmed that responding in paired subjects was associative. Although many stimuli can act as a CS in adults, the advantage of using US-US pairings is that responses to the first US ensure young rat pups are capable of detecting the stimulus-something that may not be true when auditory or visual stimuli are used early in the development of altricial animals. The US-US pairing paradigm could be used to study the ontogeny and neural substrates of learning and memory before other sensory systems mature, and evaluate learning and memory in animal models of early developmental disorders.