Synaptotagmin-7 Counteracts Short-Term Depression during Phasic Dopamine Release.

Dopamine neurons switch from tonic pacemaker activity to high-frequency bursts in response to salient stimuli. These bursts lead to superlinear increases in dopamine release, and the degree of this increase is highly dependent on firing frequency. The superlinearity and frequency dependence of dopamine release implicate short-term plasticity processes.

Fast resupply of synaptic vesicles requires synaptotagmin-3.

Sustained neuronal activity demands a rapid resupply of synaptic vesicles to maintain reliable synaptic transmission. Such vesicle replenishment is accelerated by submicromolar presynaptic Ca signals by an as-yet unidentified high-affinity Ca sensor. Here we identify synaptotagmin-3 (SYT3) as that presynaptic high-affinity Ca sensor, which drives vesicle replenishment and short-term synaptic plasticity.

Opioids differentially modulate two synapses important for pain processing in the amygdala.

Background And Purpose: Pain is a subjective experience involving sensory discriminative and emotionally aversive components. Consistent with its role in pain processing and emotions, the amygdala modulates the aversive component of pain. The laterocapsular region of the central nucleus of the amygdala (CeLC) receives nociceptive information from the parabrachial nucleus (PB) and polymodal, including nociceptive, inputs from the basolateral nucleus of the amygdala (BLA).

Dopamine and opioids inhibit synaptic outputs of the main island of the intercalated neurons of the amygdala.

Neural circuits in the amygdala are important for associating the positive experience of drug taking with the coincident environmental cues. During abstinence, cue re-exposure activates the amygdala, increases dopamine release in the amygdala and stimulates relapse to drug use in an opioid dependent manner. Neural circuits in the amygdala and the learning that underlies these behaviours are inhibited by GABAergic synaptic inhibition.

Central sensitization of the spino-parabrachial-amygdala pathway that outlasts a brief nociceptive stimulus.

Key Points: Chronic pain is disabling because sufferers form negative associations between pain and activities, such as work, leading to the sufferer limiting these activities. Pain information arriving in the amygdala is responsible for forming these associations and contributes to us feeling bad when we are in pain. Ongoing injuries enhance the delivery of pain information to the amygdala.

Endogenous opioids regulate moment-to-moment neuronal communication and excitability.

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster.