Antagonists D1 and D2 of Dopamine Receptors Determine Different Mechanisms of Neuroprotective Action in the Frog Vestibular.

The high functional plasticity of the glutamatergic synapse of the vestibular epithelium is supported by a delicate balance of excitatory and inhibitory interactions. One of the peptides co-localized with acetylcholine (ACh) in the efferent fibers is dopamine. Using external perfusion of the synaptic zone and multiunit recording of an afferent fibers activity the effect of dopamine antagonists on the background firing rate of the semicircular canal sensory fibers was studied on the isolated frog vestibular. The present research revealed that the dopamine receptor antagonist (D1) SCH-23390 significantly reduced the level of background activity at high concentrations. In contrast, D2 antagonist eticlopride caused positive-negative answer of the background activity of the sensory fibers in dose-depending manner. The data confirm the hypothesis that dopamine, being tonic released from the efferent fibers, realizes neuroprotective inhibitory control over the afferent glutamatergic synapse activity in the vestibular epithelium via D1 and D2 receptors.

Soluble Guanylate Cyclase As the Key Enzyme in the Modulating Effect of NO on Metabotropic Glutamate Receptors.

The synaptic plasticity of the afferent synapse of the vestibular apparatus is defined by the dynamic interaction of ionotropic and metabotropic glutamate receptors and the modulators of synaptic transmission. It was shown that nitric oxide modulates iGluR responses. In this paper, the effect of NO on the function of the afferent synapse mGluR was investigated. Inhibitor of nitric oxide synthase lowered the level of background activity but increased the amplitude of the responses of groups I and II mGluR agonist ACPD. Donor NO SNAP increased the level of background activity. Short-term perfusion of the synaptic region with low concentrations of SNAP led to a decrease in the amplitude of the answers of mGluR agonists ACPD and DHPG. The inhibitory effect of the NO donor was eliminated under blockade of soluble guanylate cyclase with a specific inhibitor ODQ. A prolonged application of NO did not cause a statistically significant change in the amplitude of the ACPD response. However, SNAP at concentrations of 10 and 100 µM increased the amplitude of the mGluR agonist responses 30 and 15 minutes, respectively, after termination of the NO donor exposure. The obtained data show the multidirectional effect of NO on the function of mGluR and testify to the existence of a complex modulating mechanism of the afferent flow from vestibular organs to the central nervous system.

Metabotropic glutamate receptors as targets of neuromodulatory influence of nitric oxide.

A possible effect of nitric oxide (NO) on metabotropic glutamate receptor (mGluR) function in the amino acid afferent synapse was investigated in the isolated labyrinth of the frog Rana temporaria. The modification of the amplitude of responses of metabotropic glutamate receptor agonist trans-ACPD was analyzed during bath applied NO donor S-nitroso-N-acetyl-DL-penicillamine SNAP (0.1-100 µM) or nitric oxide synthase inhibitor L-NAME. It was shown that NO donor SNAP (1 µM) inhibited mGluR induced responses, and the inhibitor of NO-synthase L-NAME (100 µM) increased the amplitude of trans-ACPD evoked answers. The results suggest that NO can depress mGluR function due to modulation of functions of the endoplasmic reticulum channels.

Dopaminergic modulation of afferent synaptic transmission in the semicircular canals of frogs.

Using multiunit recording of action potentials from the whole nerve with the aid of external perfusion, we investigated the effects of dopamine (DOP) agonists that are involved in modulatory actions on synaptic transmission in the isolated labyrinth preparations of frogs. The external application of DOP (0.1-1 mM), the D(1) agonist chloro-APB hydrobromide (CAPB, 50-100 microM) and the D2 agonist quinerolane (QUI, 50-100 microM) induced a dose-dependent and reversible decline in the resting discharge frequency. In this concentration range, the potency of applied CAPB considerably exceeded that of QUI. AMPA, NMDA and ACPD responses were inhibited by the D1 and D2 agonists, implicating both subtypes of DOP receptors in the modulation of both ionotropic and metabotropic glutamate receptors. The inhibitory action of the DOP agonists on L-glutamate responses persisted in a high Mg2+ solution in conditions of selective activation of the postsynaptic membrane. The results obtained suggest that DOP may interact with both D1 and D2 receptor subtypes, most likely located postsynaptically on the afferent nerve fibers. This dopaminergic control mechanism may result in the reduction of the activated firing rate, thus preventing over-excitation and excitotoxic injury of the afferent dendrites after the external application of L-glutamate and excessive receptor stimulation.

Compensatory plasticity of the brain under conditions of its injury.

The possibility of the utilization of the galvanic skin response (GSR) as a test for the analysis of compensatory processes under the conditions of natural compensation and with the use of functional biofeedback was studied in experiments on cats anesthetized with chloralose and immobilized with flaxedil, as well as in clinical conditions in healthy children and children suffering from childhood cerebral palsy (CCP). It was demonstrated in this study that the habituation of the GSR is disturbed in the case of unilateral brain trauma. These differences level out a year after the brain trauma. When functional biofeedback is used to accelerate habituation processes of a compensatory character, the GSR of the right and left sides of the body equalize and approximate that observed in healthy children. This study is yet another confirmation of the advantage of functional biofeedback as compared with traditional treatment methods. The data obtained also make it possible to believe that the habituation of the GSR may be useful not only for the analysis of the depth and level of the injury of nerve tissue, but for the objective assessment of compensatory restorative processes as well.

[The compensatory plasticity of the brain when it is damaged]. / Kompensatornaia plastichnost' mozga v usloviiakh ego povrezhdeniia.

A new test for determination of the degree of the compensatory processes after brain damage was proposed in experiments in the cats with one-sided transection of the hemisphere and children with one-sided cerebral palsy. The process of habituation of the skin galvanic reaction was used for this aim.