Synaptic plasticity in the avian inferior colliculus: Role of retrograde messengers

Abstract

The enduring changes in synaptic efficacy observed in vitro, such as the long-term potentiation (LTD) and long-term depression (LTD), are believed to underlie behavioral changes driven by experience. Several documented cases have shown that experience can induce changes consistent with LTP and LTD. In a well-studied case of experience-dependent plasticity in birds and mammals, the auditory midbrain has been implicated. Surprisingly, while the first reports on this phenomenon occurred over two decades ago, its synaptic bases have remained largely unexplored. The auditory midbrain, thus, offers an interesting opportunity to study how synaptic plasticity can mediate behavioral plasticity. This thesis contains the first evidence of long-term synaptic plasticity and its mechanism in the avian auditory midbrain.;We focused our studies on neurons in the external part of the midbrain auditory torus (EX) of the chicken. Using an in vitro slice preparation and patch-clamp recording, we examined the activity-dependent modulation at the synaptic connection between EX cells and their afferent input. At this synapse, we observed LTD mediated by endocannabinoids (eCB). This LTD is expressed as a coincident reduction in neurotransmitter release and a decrease in postsynaptic NMDAR-mediated current. The dual presynaptic and postsynaptic components of this LTD are mediated by Type 1 Cannabinoid receptors (CB1R) that appear located on both the pre- and postsynaptic terminals. Importantly, this effect of eCBs on postsynaptic NMDAR-mediated transmission had not been described before.;Subsequent study of this synapse unveiled a modulation of spontaneous neurotransmitter release by retrograde messengers. Specifically, we found that in addition to eCBs, glutamate appears to function as a retrograde messenger. Our results indicate that activity-dependent postsynaptic release of glutamate is responsible for a selective suppression of spontaneous neurotransmitter release onto EX neurons. This effect requires the activation of presynaptic NMDARs, adding to the growing evidence that NMDARs are presynaptically located. The suppression of spontaneous neurotransmitter release by retrograde glutamate indicates that retrograde messengers can selectively modulate action-potential dependent and spontaneous neurotransmitter release. Altogether, the results presented here not only expand on our knowledge of synaptic plasticity in the auditory pathway but also on the role of retrograde messengers in neurotransmission.