We found evidence supporting our hypothesis that glutamate, previously identified in BRNs by an immunocytological

study, is involved in bilateral coupling. First, a combination of extracellular and intracellular electrophysiological recordings revealed that both electrically and optically evoked CAPs generate excitatory synaptic potentials and action potentials in contralateral BRNs. Application of glutamate also led to increased PI3K inhibitor neuronal activity of individual BRNs both in the intact retina as well when isolated in cell culture. Lastly, glutamate-induced inward currents were characterized in cultured BRNs using perforated-patch recordings. The reversal potential was close to 0 mV, and the currents were sensitive to N-methyl-D-aspartic acid (NMDA) and non-NMDA antagonists. NMDA and AMPA, as well as aspartate, also induced distinct inward currents in BRNs. We conclude that glutamate can be used by BRNs as a transmitter to influence electrical activity in the contralateral pacemaker population.

We propose that glutamate is required for synchronizing of the bilaterally paired retinal clocks producing a unified circadian timing signal. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Rationale Neurodegenerative changes have been suggested to provide a basis for the pathophysiology of schizophrenia. T-817MA (1-1 azetidin-3-ol maleate) is a novel compound with neuroprotective and neurite-outgrowth effects, as elicited in rat primary cultured neurons.

Objectives We examined the effect of T-817MA on phencyclidine (PCP)-induced disruption of prepulse inhibition (PPI), a measure of sensorimotor Bcl-w gating, in male Wistar rats.

Materials

and methods In chronic experiments, male Wistar rats were injected intermittently with PCP (2.0 mg/kg, i.p., three times per week) or vehicle (saline, 2.0 ml/kg) for 1 month. T-817MA (0.21 or 0.07 mg/ml, p.o.) or distilled water was administered throughout the study period. In an acute experiment, T-817MA (8.4 mg/kg, p.o.) or distilled water was administered, followed by treatment with PCP (2.0 mg/kg, i.p.) or vehicle (saline, 2.0 ml/kg), before PPI measurements.

Results Intermittent administration of PCP for 1 month induced persistent disruption of PPI. Coadministration of T-817MA at 0.21 mg/ml but not 0.07 mg/ml completely blocked PCP-induced disruption of PPI, whereas T-817MA (0.21 mg/ml) by itself did not show a significant effect on PPI in control rats. On the other hand, single administration of T-817MA did not affect PPI disruption by acute treatment with PCP.

Conclusions These results suggest that T-817MA is effective in ameliorating sensorimotor gating deficits caused by chronic PCP treatment, possibly via neuroprotective actions. Our findings provide a novel therapeutic approach for patients with schizophrenia.