Factors affecting the synaptic plasticity of hippocampus
Mathilakath Keralapurath, Madhusudhanan
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Involvement of the hippocampus in learning and memory is well known. Despite maintaining a uniform intrinsic circuitry throughout the structure, there are evidences for significant functional differences between the septal (dorsal) and temporal (ventral) sectors of hippocampus. Appreciation for the role of ventral hippocampus in the emotive and reward associated behaviors is on the rise. Behavioral and lesion studies in rodents have suggested that hippocampus plays an important role in drug reinstatement behaviors, although confirmatory molecular and electrophysiological evidences are lacking in this aspect. To study the effects of cocaine, we employed either the locomotor sensitization protocol where the drug was non-contingently administered by the experimenter, or we utilized the self-administration protocol where the rats were allowed to voluntarily administer drugs. Additionally, hippocampal feedback regulation of the hypothalamus-pituitary-adrenal axis is critical in the body’s response to stress. We investigated the effects of minor stressors such as novelty, handling and i.p. injections associated with a locomotor sensitization protocol on the hippocampal synaptic plasticity. We found that the minor, intermittent stressors associated with commonly employed behavioral protocols were sufficient to induce persistent stress-like effects. Cocaine, either experimenter administered or self-administered by the rats, specifically altered synaptic properties in the ventral hippocampus, albeit in different ways. Non-contingent cocaine exposures acted as metaplastic triggers and persistently enhanced the artificially induced LTP in the ventral hippocampus for at least 2 weeks after the last injection. In contrast, cocaine self-administration resulted in persistent enhancement of basal synaptic transmission in the ventral hippocampus, with both increases in excitatory glutamatergic activity and suppression of GABAergic inhibition being observed. Unlike in the non-contingently exposed groups, cocaine self-administration resulted in the suppression of LTP in the ventral hippocampus, suggesting a causal link between impaired learning and addicted states observed in the human subjects. Increased sensitivity of the ventral sector of the hippocampus to stress and drugs of abuse indicate its importance in the neuronal circuitry as a key intersection point where these co-morbidities of stress and drugs of abuse overlap.