RIM1α-deficient synapses show structural defects in presynaptic vesicle distribution and tethering to the active zone that can be reversed by proteasome inhibition.

2؉ signaling in astrocytes for control of blood flow is demonstrated by SNAP 5114-sensitive constriction of blood vessels accompanying GABA uptake. The results suggest that GABAergic signaling is composed of GABA uptake-mediated Na ؉ rises that reduce Na ؉ /Ca 2؉ exchange, thereby leading to a Ca 2؉ increase sufficient to trigger Ca 2؉ -induced Ca 2؉ release via InsP3 receptors. Hence, GABA transporters not only remove GABA from the extracellular space, but may also contribute to intracellular signaling and astrocyte function, such as control of blood flow.calcium-induced calcium release ͉ GABA transporter ͉ Neuron-glia interaction ͉ sodium imaging ͉ vasoconstriction

The cannabinoid receptor type 1 (CB1) and the central nucleus of the amygdala (CeA) are both known to have crucial roles in the processing of fear and anxiety, whereby they appear to be especially involved in the control of fear states. However, in contrast to many other brain regions including the cortical subregions of the amygdala, the existence of CB1 in the CeA remains enigmatic. In this study we show that CB1 is expressed in the CeA of mice and that CB1 in the CeA mediates short-term synaptic plasticity, namely depolarization-induced suppression of excitation (DSE) and inhibition (DSI). Moreover, the CB1 antagonist AM251 increased both excitatory and inhibitory postsynaptic responses in CeA neurons. Local application of AM251 in the CeA in vivo resulted in an acutely increased fear response in an auditory fear conditioning paradigm. Upon application of AM251 in the basolateral nucleus of the amygdala (BLA) in an otherwise identical protocol, no such acute behavioral effects were detected, but CB1 blockade resulted in increased fear responses during tone exposures on the subsequent days. Moreover, we observed that the efficacy of DSE and DSI in the CeA was increased on the day following fear conditioning, indicating that a single tone-shock pairing resulted in changes in endocannabinoid signaling in the CeA. Taken together, our data show the existence of CB1 proteins in the CeA, and their critical role for ensuring short-term adaptation of responses to fearful events, thereby suggesting a potential therapeutic target to accompany habituation-based therapies of post-traumatic symptoms.

Purinergic receptors play a key role in neuron-glia and glia-neuron interactions. In the present study, we have recorded cytosolic Ca(2+) responses using confocal imaging in astrocytes of acute olfactory bulb slices from mice (postnatal days 3-8). By application of agonists and antagonists, we identified two types of receptors, P2Y(1) and A(2A), that mediated Ca(2+) responses attributable to Ca(2+) release from intracellular stores in the astrocytes. Both receptor types were activated by application of ATP and ADP; however, when enzymatic ATP degradation was suppressed by the alkaline phosphatase inhibitor levamisole, ATP only activated MRS2179-sensitive P2Y(1) but not ZM241385-sensitive A(2A) receptors. The dose-response curve for A(2A) receptors activated by adenosine revealed an EC(50) of 0.3 microM, one order of magnitude smaller than the EC(50) of 5 microM determined for P2Y(1) receptors activated by ADP. Electrical stimulation of the olfactory nerve in the presence of glutamate receptor blockers to suppress excitation of postsynaptic neurons evoked Ca(2+) responses in most of the astrocytes, which were inhibited by blocking both P2Y(1) and A(2A) receptors. Our results indicate that olfactory nerve terminals release not only glutamate, but also ATP, which activates P2Y(1) receptors and, after degradation of ATP to adenosine, A(2A) receptors in astrocytes.