Age-dependent changes in the functional expression of two nicotinic receptor subtypes in CA1 stratum radiatum interneurons in the rat hippocampus

Abstract

Protein density measurements and mRNA analysis have provided valuable information on age-dependent changes in the distribution of different nicotinic receptor (nAChR) subtypes in various areas of the rat brain, including the hippocampus. However, very little is known regarding the functional expression of nAChRs in individual neuron types at various ages. Likewise, there is paucity of information regarding the functional and pharmacological profile of nAChRs in the mature rat hippocampus. To address these issues, we used the whole-cell patch-clamp technique to record nicotinic responses from CA1 stratum radiatum (SR) interneurons in hippocampal slices from rat pups (5–19 days old) and adult rats (2–5 months old). As previously observed in the hippocampus of rat pups, CA1 SR interneurons in the hippocampus of adult rats responded to choline (10 mM, 12 s) with whole-cell currents that decayed to the baseline within the agonist pulse, were sensitive to inhibition by methyllycaconitine (10 nM) or α-bungarotoxin (50 nM), and were, therefore, mediated by α7* 1 1 According to the nomenclature for nAChRs and their subunits [Lukas RJ, Changeux JP, Le Novere N, Albuquerque, EX, Balfour DJ, Berg, DK et al. International Union of Pharmacology. XX. Current status of the nomenclature for nicotinic acetylcholine receptors and their subunits. Pharmacol Rev 1999; 51: 397–401.], the asterisk next to nAChR subunits throughout text is meant to indicate that the exact subunit composition is not known. [1] nAChRs. Likewise, as previously observed in the hippocampus of young rats, in the adult rat hippocampus excitatory postsynaptic currents (EPSCs) were recorded from SR interneurons in response to a pulse of ACh (0.1 mM, 12 s) applied in the presence of the GABA A receptor antagonist bicuculline. ACh-triggered EPSCs were inhibited by mecamylamine (1 μM) or choline (1 mM) and were, therefore, likely to have resulted from activation of α3β4β2* nAChR. The magnitude of α7* nAChR-mediated responses increased with the age of the animals. In contrast, the magnitude of α3β4β2* nAChR-mediated responses was highest at the second postnatal week. The distinct age dependency of functional expression of α7* and α3β4β2* nAChRs strongly suggests that the excitability of CA1 SR interneurons is differentially regulated by the nicotinic cholinergic system in the hippocampus of rat pups and adult rats.