NMDA receptor blockade alters the intracellular distribution of neuronal nitric oxide synthase in the superficial layers of the rat superior colliculus

Nitric oxide (NO) is a molecular messenger involved in several events of synaptic plasticity in the central nervous system. Ca2+ influx through the N-methyl-D-aspartate receptor (NMDAR) triggers the synthesis of NO by activating the enzyme neuronal nitric oxide synthase (nNOS) in postsynaptic densities. Therefore, NMDAR and nNOS are part of the intricate scenario of postsynaptic densities. In the present study, we hypothesized that the intracellular distribution of nNOS in the neurons of superior colliculus (SC) superficial layers is an NMDAR activity-dependent process. We used osmotic minipumps to promote chronic blockade of the receptors with the pharmacological agent MK-801 in the SC of 7 adult rats. The effective blockade of NMDAR was assessed by changes in the protein level of the immediate early gene NGFI-A, which is a well-known NMDAR activity-dependent expressing transcription factor. Upon chronic infusion of MK-801, a decrease of 47 percent in the number of cells expressing NGFI-A was observed in the SC of treated animals. Additionally, the filled dendritic extent by the histochemical product of nicotinamide adenine di-nucleotide phosphate diaphorase was reduced by 45 percent when compared to the contralateral SC of the same animals and by 64 percent when compared to the SC of control animals. We conclude that the proper intracellular localization of nNOS in the retinorecipient layers of SC depends on NMDAR activation. These results are consistent with the view that the participation of NO in the physiological and plastic events of the central nervous system might be closely related to an NMDAR activity-dependent function.

The superior colliculus, a neuronal network resistant to the Gaba withdrawal syndrome

Chronic intracortical perfusion of GABA (Gamma Amino Butyric Acid) and its subsequent withdrawal generates, the GABA withdrawal syndrome (GWS). This particular epileptic model has been observed in the motor cortex of monkeys and rats. Our purpose was to study the GWS in the motor cortex (MC), dorsal hippocampus (DH), and superior colliculus (CS). Thirty chronically-implanted adult Wistar rats were separeted into 3 groups of 10 (8 experimental and 2 controls). The first group received GABA in MC, the second in the DH and the third in the SC. GABA was released in doses of 10 to 60 mug/mul/h for 6 days employing osmotic mini-pumps. Two control rats per group received saline solution in the above-mentioned structures. Rats perfused in the MC showed GWS after interruption of the GABA flow. The group perfused in the DH showed paroxysmal discharges and epileptic seizures during perfusion. They also later showed GWS. No epileptic effects were observed in the SC-perfused group during either the GABA perfusion or during withdrawal. None of the six control animals showed epileptic effects. Our results show that the SC offers a strong resistance to GWS. This could be explained by the particular neuronal network structure of rat SC.