The medial septum (MS) and the diagonal band (DB) have cholinergic and GABAergic neurons projecting to the hippocampus. Afferent fibres that use diverse neurotransmitters determine its activity, which is concerned with the hippocampal theta rhythm generation and learning and memory processes. Preliminary outcome suggests that some of these connections could be modulated, even though the neurotransmitters involved have not been clearly defined. The aim of the present work is to characterize the glutamatergic neurotransmission in the MS and its modulation through some other neurotransmitters.

Adult Wistar rats were deeply anaesthetized and decapitated, and their brain extracted to prepare slices of 300 µm containing MS and BD (Yajeya et al.). After 1-3 h of incubation the slices were transferred to an immersed recording chamber. The perforated patch clamp technique was used with gramicidin or anfotericin in the patch pipette to obtain the whole cell configuration. Excitatory evoked postsynaptic currents (EPSC) generated by DB stimulation were recorded at -60 or -70 mV voltage clamp potential. Analysis was done by the Mini Analysis program 5.2 of Synaptosoft.

Forty-five neurons were recorded. DB stimulation evoked an inward current of variable amplitude depending on the stimulus intensity. Perfusion with D-AP5 (50 µM) generated a significant decrease (P ²le³ 0.05) in the amplitude (n = 10) of the current, which was completely blocked by CNQX (10 µM) suggesting that its was mediated through glutamic acid acting on AMPA/kainate and NMDA receptors. Perfusion with GABA (20 µM) also decreased the excitatory current (n = 6), an effect which was reversed or even inverted by bicuculline (10 µM) perfusion. This result suggests a modulatory effect through GABA_A receptors. On the other hand, the current amplitude was decreased under perfusion with D-tubocurarine (2 µM) (n = 6) or atropine (5 µM) (n = 5), indicating that acetylcholine acting on nicotinic or muscarinic receptors could control glutamic neurotransmission in the MS. In order to determine the pre- or postsynaptic location of acetylcholine effect, a paired pulse protocol was used. PP-ratio for control (S₂/S₁) was 1.283, meanwhile PP-ratio for atropine was 1.056. The observed results support that the acetylcholine could act in both locations. The different possibilities described concerning the modulation of glutamic neurotransmission in the MS could be related to the topographic projections of the septum towards other areas of nervous system.

Yajeya I et al. (1997). Neuroscience 78, 731-743.

This work was supported by grants PBI2000-11900 (DGICYT) and 01/0385 (FIS). The authors is supported by an AECI fellowship.