Characterisation of rat superficial superior colliculus neurones: firing properties and sensitivity to GABA

Abstract

Physiological, pharmacological and morphological properties of superficial superior colliculus neurones ( n=93) were characterised using whole-cell patch-clamp recordings in rat brain slices. Six cell types (narrow- and wide-field vertical, horizontal, piriform, marginal and stellate) were identified based on Lucifer Yellow labelling but no cell type-specific spike pattern could be identified. Resting membrane potentials were homogeneous (mean: −67.1±0.7 mV, n=48), and spike frequencies ranged from 10 to 70 Hz (80 pA current injection). About 66% of the cells displayed regular and sustained spike production, throughout all neuronal categories. Rebound spikes and spontaneous activity were observed frequently in all cell types. Synaptically evoked action potentials appeared as single spikes (mean amplitude: 76.0±3.2 mV, n=34) followed by a fast after-hyperpolarising potential (mean amplitude: 25.4±1.4 mV, n=34) and variable late potentials (late after-depolarising and/or -hyperpolarising). Pharmacologically, a characterisation using GABA and its subtype-specific agonists indicated a strong inhibitory influence of this transmitter system on >90% of cells. The GABA A receptor agonist, 4,5,6,7-tetrahydroisoxazolo[5,4- c]pyridin-3-ol (100 μM), caused a reversible hyperpolarisation (∼9 mV) and spike inhibition of all neurones studied. This was more pronounced for intrinsic than for synaptically evoked spikes. Assessment of the GABA C receptor agonist, cis-4-aminocrotonic acid (1 mM), also revealed a hyperpolarisation (∼3 mV) and an inhibitory action on firing, but this was not as potent and homogeneous, compared to the GABA A receptor agonist. Further, the GABA B receptor agonist, baclofen (50–100 μM), had more variable (hyperpolarising, depolarising or no change) effects on the membrane potential. It showed little modulation of current-induced action potentials but fully blocked synaptic spikes. Assessment of GABA receptor antagonist actions revealed the presence of weak tonic and strong phasic GABA A receptor-mediated inhibition in the superficial superior colliculus: application of the GABA A receptor antagonist, bicuculline (100 μM), led to a generally enhanced excitability and depolarisation (∼5 mV). Intrinsic firing was somewhat enhanced, but synaptic spiking was drastically potentiated and prolonged. In contrast, 1,2,5,6-tetrahydro-(pyridin-4-yl) methylphosphinic acid (TPMPA; 100 μM), the GABA C receptor antagonist, produced little effect on these physiological parameters. The GABA B receptor antagonist, CGP35348 (200 μM), caused a partial inhibition of late after-hyperpolarising potentials (∼30%). Uptake of GABA contributes little to endogenous inhibition in the superior colliculus slice preparation, as suggested by the action of GABA uptake inhibitors SKF89976 (50–100 μM) and nipecotic acid (200–500 μM), both had no obvious effect on physiological parameters. However, in the presence of these compounds, sub-maximal inhibitory actions of GABA were potentiated. In conclusion, different cell types in the superficial superior colliculus do not display distinct physiological properties and are subject to strong inhibitory modulation. We therefore suggest that signal processing in this brain region does not require cell type-specific encoding of information. In line with evidence provided by previous in vivo investigations, identification of visual stimuli and orientation responses appears to be realised via the network properties of the receptive fields that form topographic maps.