Effect of early isolation on the synaptic function in the dentate gyrus and field CA1 of the guinea pig.

Abstract

We previously reported that neonatal isolation shapes neuron morphology remarkably in the dentate gyrus and hippocampus of the guinea pig, a precocial rodent whose brain is at an advanced stage of maturation at birth. The aim of the present work was to investigate the effects of early isolation on the physiology of the hippocampal trisynaptic circuit. Male and female guinea pigs were assigned at 6-7 days of age to either a social or an isolated environment. After 90-100 days, the animals were anesthetized and electrophysiological experiments were carried out. The monosynaptic response evoked by medial perforant path stimulation in the dentate gyrus (DG) and the following response trisynaptically evoked in field CA1 by the DG-CA3 system were evaluated with several stimulus protocols: (1) current source-density (CSD) analysis; (2) input/output function; (3) paired-pulse potentiation (PPP); and (4) long-term potentiation (LTP). Isolated animals exhibited a reduction in the magnitude of the current sinks in the middle molecular layer and granule cell layer of the DG and in the input/output function of the granule cell population excitatory postsynaptic potential (EPSP) and population spike (PS) over a wide range of stimuli. The latter effect was larger in males. The ratio between the PS and EPSP of the granule cells was reduced in isolated compared to control males, but the opposite occurred in females. Isolation affected PPP of the granule cell response in males only, causing a larger facilitation of the PS. No isolation-related effects were found in the magnitude of the LTP of the DG response in either sex. Isolated animals exhibited a reduction in the current sinks in stratum radiatum and stratum pyramidale of field CA1 and in the input/output function of the EPSP and PS of field CA1. These effects were larger in males. The results show that early isolation causes a reduction in the synaptic function of the DG-CA3-CA1 system, driven by perforant path volleys. The isolation-induced impairment in signal processing along the hippocampal network suggests that the outcome of early isolation may be an impairment in the memory functions in which the entorhinal-hippocampal system plays a key role.