Modulation of basal glutamatergic transmission by nicotinic acetylcholine receptors in rat hippocampal slices

ABSTRACT

Nicotinic acetylcholine receptors [nAChRs] regulate epileptiform activity and produce a sustained proepileptogenic action within the hippocampal slices. In the present study, we investigated the effect of nAChRs on evoked glutamatergic synaptic transmission in area CA3 and CA1 of rat hippocampal slices to identify possible excitatory circuits through which activation of nAChRs produce their pro-epileptogenic effects. Hippocampal slices [400 micro m thick] prepared in vitro from male Wistar rats [3-5 weeks], using standard procedures. Following 1 hr equilibration in artificial cerebrospinal fluid [ACSF], slices transferred to an interface recording chamber. Stimulatory electrodes placed within the hilus or Schaffer-collateral pathways and extracellular field recordings made in the stratum radiatum of the CA1 and CA3 regions to investigate evoked synaptic responses. Bath application of the selective nAChR agonist dimethylphenyl-piperanzinium [DMPP, 30 micro M] resulted in a sustained and reversible enhancement of glutamate afferent evoked fEPSP amplitude by 15.7 +/- 5.1% [mean +/- SEM; n = 8 of 12] in the CA3 region of the hippocampus but not in the CA1 [-5.25 +/- 8.3%, mean +/- SEM; n = 5]. Activation of nAChRs may produce pro-epileptogenic actions in part through regulating glutamatergic circuits. Difference in nAChR regulation is also evident between different regions of hippocampus