Strain-Specific Nicotinic Modulation of Glutamatergic Transmission in the CA1 Field of the Rat Hippocampus: August Copenhagen Irish Versus Sprague-Dawley

Abstract

Prepulse inhibition (PPI), a measure of sensorimotor gating impaired in patients with schizophrenia, is more sensitive to disruption by apomorphine in prepubertal August Copenhagen Irish (ACI) than Sprague-Dawley (SD) rats. In brain regions including the hippocampus, PPI is modulated by α7* nicotinic receptors (nAChRs) and kynurenic acid (KYNA), a kynurenine metabolite that blocks α7 nAChRs. Here, KYNA levels and nAChR activities were measured in the hippocampi of 10- to 23-day-old ACI and SD rats of both sexes. Hippocampal KYNA levels were not different between ACI and SD rats. In hippocampal slices from both rat strains, choline (10 mM) evoked α7* nAChR-mediated type IA currents in CA1 stratum radiatum (SR) interneurons. In the presence of α7 nAChR antagonists, acetylcholine (ACh, 1 mM) evoked α4β2* nAChR-mediated type II currents. ACh also triggered excitatory postsynaptic currents (EPSCs) that resulted from α3β4* nAChR activation in glutamatergic neurons/axons synapsing onto the interneurons. The magnitude of the nicotinic responses did not differ significantly between male and female rats. Only the magnitude of α3β4* nAChR responses and the frequency of spontaneous EPSCs recorded from CA1 SR interneurons differed between the rat strains, being significantly larger in ACI than SD rats. These results indicate that the α3β4* nAChR activity in glutamatergic neurons/axons and the number of glutamatergic terminals synapsing onto CA1 SR interneurons are larger in prepubertal ACI than SD rats. The differential sensitivity of these rats to PPI disruption by apomorphine may result from strain-specific levels of glutamatergic activity and its strain-specific modulation by α3β4* nAChRs in the hippocampus.