The magnitude of alpha7 nicotinic receptor currents in rat hippocampal neurons is dependent upon GABAergic activity and depolarization.

Hippocampal alpha7(*) nicotinic acetylcholine receptors modulate the release of GABA and glutamate. The control of functional receptor pools by cell firing or synaptic activity could therefore allow for a local adjustment of the sensitivity to cholinergic input upon changes in neuronal activity. We first investigated whether tonic depolarization or cell firing affected the function of alpha7(*). The amplitude of alpha7(*)-gated whole-cell currents in cultured rat hippocampal neurons exposed to high-extracellular K(+) (40 mM KCl) for 24 to 48 h increased 1.3 to 5.5 times. The proportion of alpha7(*)-responsive neurons (99%), the potency of acetylcholine, and the sensitivity to nicotinic antagonists were all unaffected. In contrast, block of spontaneous cell firing with tetrodotoxin for 24 h led to a 37% reduction in mean current amplitude. Reduced alpha7(*) responses were seen after a 24-h blockade of N-type calcium channels but not of L-type calcium channels, N-methyl-d-aspartate (NMDA), or non-NMDA receptor channels, protein kinase C, or calcium-calmodulin kinases II and IV. The N-type or L-type calcium channel antagonists omega-conotoxin GVIA and nifedipine did not prevent the current-potentiating effect of KCl. The GABA(A) antagonist picrotoxin led to a 44% reduction of the currents, despite increasing action potential firing, and also reversed the potentiating effect of KCl. Treatment with GABA, midazolam, or a GABA uptake blocker led to increased currents. These data indicate that alpha7(*)-gated currents in hippocampal neurons are regulated by GABAergic activity and suggest that depolarization-induced GABA release may underlie the effect of increased extracellular KCl.

Spine density and dendritic branching pattern of hippocampal CA1 pyramidal neurons in neonatal rats chronically exposed to the organophosphate paraoxon.

The organophosphate cholinesterase (ChE) inhibitor paraoxon is the oxidized active metabolite of parathion, a pesticide whose use in agriculture has been matter of increasing concern. The present work was aimed at reproducing a prolonged exposure to low concentrations of paraoxon and assessing possible damage to the hippocampus during the period of most significant cholinergic development. Male Wistar rats were given, from P8 to P20, subcutaneous daily injections of paraoxon (0.1, 0.15 and 0.2mg/kg). The rate of body weight gain was reduced by all doses of paraoxon and brain ChE activity progressively decreased up to 60% by P21. Some deaths occurred in the beginning of the treatment, but the surviving animals showed neither convulsions nor overt signs of cholinergic hyperstimulation. Morphometric analysis of Lucifer Yellow-stained CA1 pyramidal neurons in coronal sections of the hippocampus showed that by P21 paraoxon caused a decrease in spine density on basal but not on secondary apical dendrites. The dendritic arborization and the pyramidal and granular cell body layers were not altered by paraoxon. ChE staining decreased in all hippocampal and dentate gyrus regions studied, whereas choline acetyltransferase (ChAT) and zinc-positive fibers remained as in control. In summary, chronic exposure to low paraoxon concentrations during the period of rapid brain development caused significant and selective decrease in basal dendritic spine density of the CA1 pyramidal neurons. Distinct modulation of the basal tree at the stratum oriens by the interplay of cholinergic afferent and GABAergic interneurons, as well as the remodeling process in response to a repetitive and rather mild paraoxon insult, may account for this selective susceptibility of basal dendritic spines. The hippocampal alterations described here occurred in the absence of toxic cholinergic signs and may affect brain development and cause functional deficits that could continue into adulthood.

Patters of nitric oxide synthase expression in the developing superior colliculus

Nitric oxide (NO) is synthesized in cells of both the central and peripheral nervous system and has been implicated in several forms of synaptic plasticity. The enzyme that produces NO, nitric oxide synthase (NOS), can be visualized in the brain by the reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry technique (NADPH-d). We have used NADPH-d activity to detect the presence of NOS-positive cells in the developing rat superior colliculus. Our results showed that NOS is present in cells and neuropil in the developing and adult rat superior colliculus. The first NOS-positive cells appeared at postnatal day 7 and were weakly stained. The number and intensity of the NOS-positive cells increased progressively during the following days reaching a maximum at postnatal day 15. By the end of the third postnatal week, both the number and intensity of stained cells showed an adult-like pattern. The NOS-positive cells showed a Golgi-like mosphology and we have found that all cell types present in the superior colliculus express the enzyme. The expression of NOS by tectal cells parallels the functional development of the retino-collicular and cortico-tectal projections and suggest that nitric oxide synthase-positive cells might be involved in this process. In this review we highlighted some of the recent descriptions of the expression of NOS in the mammalian visual system with emphasis in the superior colliculus and correlate these findings with several developmental events taking place in this structure.