Alterations in synaptic transmission and plasticity in area CA1 of adult hippocampus following developmental hypothyroidism

Abstract

Transient reductions in thyroid hormone during critical periods of brain development can have devastating and irreversible effects on neurological function. The hippocampus is a brain region sensitive to thyroid hormones and is a necessary substrate for some forms of learning and memory. Subregions within the hippocampus display distinct ontogenetic profiles and have shown differential vulnerability to some indices of thyrotoxic insult. Synaptic function can be readily assessed in the hippocampus, yet little information exists on the consequences of early thyroid hormone insufficiency on the neurophysiological integrity of this structure. Previous work has examined the long-term consequences of perinatal hypothyroidism on neurophysiology of the dentate gyrus of the hippocampal formation. The current study reveals that alterations in synaptic function also exist in area CA1, and some differences in the pattern of effects are evident between the two hippocampal subfields. Developing rats were transiently exposed to the thyrotoxicant, propylthiouracil (PTU; 0 or 15 ppm), through the drinking water of pregnant dams beginning on gestational day 18. This regimen markedly reduced circulating levels of thyroid hormones and stunted pup growth. PTU exposure was terminated on postnatal day (PN) 21 and electrophysiological assessments were conducted by recording field potentials in area CA1 of hippocampal slices derived from adult male offspring. Synaptic transmission, short-term, and long-term synaptic plasticity were assessed. Consistent with observations in the dentate gyrus, somatic population spike amplitudes were reduced in assessments of baseline synaptic transmission of slices from PTU-exposed animals. No differences were identified in excitatory postsynaptic potentials (EPSP). Short-term plasticity of the EPSP as indexed by paired pulse facilitation was markedly impaired by PTU exposure. Long-term potentiation (LTP) of the population spike was enhanced, consistent with findings in dentate gyrus, but no change in EPSP LTP was detected. Perturbations in synaptic function in the hippocampus of adult rats transiently exposed to a period of hormone insufficiency during the perinatal period are likely to contribute to cognitive deficits associated with developmental hypothyroidism.