Inhibition of Dendritic L-Type Calcium Current by Memantine in Frog Tectum

The aim of the study was to explore the effects of memantine on responses elicited in the frog tectum by the bursts of spikes of moderate strength of a single retina ganglion cell and to gain an insight about the effect of memantine on the L-type Ca2+ current. Material and Methods. The experiments were performed in vivo on adult frogs (Rana temporaria). An individual retina ganglion cell (or its retinotectal fiber) was stimulated by current pulses delivered through a multichannel stimulating electrode positioned on the retina. Responses to the discharge of a single retinal ganglion cell were recorded in the tectum by an extracellular carbonfiber microelectrode positioned in the terminal arborization of the retinotectal fiber in the tectum layer F. The solution of memantine (1-amino-3,5-dimethyladamantane) hydrochloride (30 or 45 μM) was applied onto the surface of the tectum by perfusion at a rate of 0.4 mL/min. Results. Memantine (30–45 μM) largely inhibited the L-type Ca2+ channel-mediated slow negative wave and late discharges seen in the tectum responses without any effect on fast synaptic retinotectal transmission. Conclusions. Our results suggest that the neuroprotective effect of memantine could arise not only through the inhibition of the NMDA receptor current but also through the suppression of the L-type Ca2+ current.

N-cholinergic facilitation of glutamate release from an individual retinotectal fiber in frog

Nicotinic acetylcholine receptors are localized on retinotectal axons' terminals in lower vertebrates. The effects of activation of these receptors by endogenous acetylcholine were observed under stimulation of mass optic fibers. This study was designed to determine whether endogenous acetylcholine facilitates frog retinotectal transmission, provided only the synapses of an individual optic axon are activated, and to evaluate the feasible extent of nicotinic facilitation in these synapses by applied agonist. To this end, the effects of cholinergic drugs on the extracellular action and synaptic potentials recorded from the terminal arborization of a separate retinotectal fiber (in layer F of the tectum) were investigated in vivo. Glutamatergic nature of retinotectal synapses was reexamined by treatment with kynurenic acid. Both kynurenic acid (0.25–1 mM) and d-tubocurarine chloride (10–15 μM) significantly depressed the synaptic potentials. Carbamylcholine chloride (50–150 μM) evoked a large augmentation of the synaptic potentials and a slight but statistically significant decrease of the action potentials. D-tubocurarine reduced the effect of carbamylcholine. Pilocarpine hydrochloride (50 μM) had only a weak effect. The paired-pulse facilitation of the synaptic potentials changed significantly under the action of carbamylcholine and d-tubocurarine. The obtained results suggest that the glutamate release from activated synapses of individual retinotectal axons is facilitated by endogenous acetylcholine via presynaptic nicotinic receptors. Under used stimulation conditions, this modulation mechanism was employed only partially since its activation by applied carbamylcholine could enhance synaptic transmission up to 2.8 times.

Neonatal administration of the neurotoxin 5,7-dihydroxytryptamine results in synaptic reorganization in the superficial gray layer of the hamster's superior colliculus

Neonatal subcutaneous administration of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to hamsters results in a marked depletion of serotonin (5-HT) in cortex and an increase in the concentration of this amine in the superior colliculus (SC). To determine whether this increase was associated with an alteration in the synaptic organization of 5-HT-containing axons in the superficial gray layer of the SC, immunocytochemistry was combined with electron microscopy. In normal adult hamsters, only 4.0% of 500 5-HT-immunoreactive profiles make synaptic contacts in the superficial gray layer of the hamster's SC. In 5,7-DHT-treated animals, examination of 400 individual profiles indicated that 25.5% of 5-HT-positive profiles made synaptic contacts (P < 0.05). Given the recently demonstrated effect of 5-HT on retinotectal transmission in this species, the present results suggest that the functional organization of the SC may also be markedly altered in animals that sustain neonatal 5,7-DHT administration.