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Zusammenfassung:
In macaques, cholinergic subreceptors of nicotine (nAChRs) are predominantly found in the excitatory afferents of the primary visual cortex (V1, layer 4c) originating from the lateral geniculate nucleus (LGN). This strategic termination pattern allows nicotine to up regulate thalamocortical activity, while in parallel activity outside layer 4c can be down regulated by nicotinic effects on GABAergic inhibition. In addition to this gain-modulating role, nicotine has also distinct neuroprotective effects. Here, we have examined whether such neuroprotective effects could be at least partially explained by the gain modulation itself which tunes neuronal networks to a most efficient input-output mode with little other interferences. We investigated nicotinic effects (systemic: 0.2mg/kg) in V1 by neurophysiological recordings using multi-laminar probes and sampling of intracortical glutamate, GABA and glutamine by microdialysis in anesthetized non-human primates. Multi unit activity (MUA: 900-3200 Hz) and gamma (65-120 Hz) activity showed an improved signal-to-noise ratio (SNR) while theta activity (4-8Hz) was significantly reduced (p<0.5). The neurochemical analysis on the other hand showed increased concentrations of GABA (+40) while glutamate (-60) and glutamine levels (-50) were reduced. Taken together nicotine shifts the ratio between glutamate and GABA clearly to GABA inducing inhibitory effects which reduce excitation and result in low glutamate levels. The decrease in excitatory neuronal activity is reflected in the reduced theta activity and the improved SNR in MUA and the gamma band resulting in an efficient input-output relation due to little excitatory interferences. The low levels of glutamine are most likely caused by the increased synthesis of GABA for which glutamine is a metabolic precursor. The neuroprotective effects of nicotine can be explained by the reduction of glutamate sparing neuronal networks from abundant excitatory activity resulting in excitotoxic effects by glutamate itself and other potentially toxic metabolites.
