The Hippocampus as a Learning Machine

Year: 1973 DOI: 10.7907/P1SD-Z263
A series of experiments were conducted with the purposes of describing a functional pathway in the rat hippocampus, characterizing some conditions necessary for activating it, and identifying critical steps in this pathway. In all experiments a classical conditioning paradigm was used and the responses of units in the hippocampus and related forebrain structures to the conditioned stimulus were measured. In the first experiment a few differences between dentate, CA-3, and CA-1, the main fields of the hippocampus, were found. Units in the dentate were first to acquire a conditioned response, CA-3 followed and CA-1 was last. This order fits with the anatomical pathway. However, dentate responses were phasic, that is, did not outlast the CS-US interval, and were not specific to the conditioned stimulus. The responses of CA-3 and CA-1 units, on the other hand, were sustained and specific. The second experiment was devoted to the analysis of conditioned response latencies, in the hippocampus as well as in septum, subiculum, cingulate, entorhinal, and related structures, all known to be input stages to the hippocampus. In this experiment unconditioned short response latencies were found in the medial septum, one of the afferents of the hippocampus. These were not changed in the process of learning. The shortest conditioned response latencies were found in area CA-3 of the hippocampus. Units in area CA-1 followed, but units in dentate did not precede those of CA-3. Units in entorhinal cortex, the other main afferent to the hippocampus did not seem to precede hippocampal units either. The special relations between the hippocampus and the dentate were demonstrated in another part of this experiment, where dentate units lost their conditioned responses, in the process of extinction, before those of CA-3 and CA-1. It was postulated that septal input triggers CA-3 responses and these would be maintained in the presence of reinforcing dentate and entorhinal inputs.

The relations between the dentate and the hippocampus were further studied in two experiments in which aversive electric shock served as an unconditioned stimulus. In experiment 3 food and shock served as unconditioned stimuli on alternate days. In experiment 4 food and shock were presented in the same sessions as unconditioned stimuli to two different CS's. Dentate units had an excitatory conditioned response to a food signal and an inhibitory conditioned response to a shock signal in both experiments. Hippocampal units had excitatory responses to both signals. Acquisition of a conditioned response was not demonstrated within the hippocampus when the conditioned stimulus preceded shock and was slow when food or shock were applied following two different signals in the same session. However, when first trained that a signal precedes food, the conditioned response would be maintained in the hippocampus even if shock is now the US. The dentate is probably involved in the initiation of a conditioned response in the hippocampus but not in the maintenance of it.

A sensory-sensory paradigm (experiment 5) has demonstrated the presence of unconditioned unhabituated sensory responses in two of the afferents to the hippocampus, that is, the medial septum and the cingulate cortex. It failed to show signs of conditioning in the hippocampus proper. It was proposed that in the absence of an appetitive reward and the activity of the entorhinal-dentate pathway, conditioned responses in hippocampus cannot be established.

Conditioned entorhinal responses (experiment 6) had long latency but also long time constant. Their evoked activity was maintained for periods as long as one minute. It was found that hippocampal responses were larger, if the conditioned stimulus was applied within one minute from the previous trial. Hence, a correlation between hippocampal responses and entorhinal firing rate was demonstrated. On the basis of these experiments it was proposed that septal input enters the hippocampus at the CA-3 area, is able to selectively activate these cells only in the presence of facilitation produced by entorhinal and dentate activity. The facilitatory entorhinal activity is triggered mainly by positive reward.