PKC-mediated GABAergic enhancement of dopaminergic responses: implication for short-term potentiation at a dual-transmitter synapse

Abstract

Svensson E, Proekt A, Jing J, Weiss KR. PKC-mediated GABAergic enhancement of dopaminergic responses: implication for short-term potentiation at a dual-transmitter synapse. J Neurophysiol 112: 22-29, 2014. First published April 9, 2014 doi:10.1152/jn.00794.2013.-Transmitter-mediated homosynaptic potentiation is generally implemented by the same transmitter that mediates the excitatory postsynaptic potentials (EPSPs), e.g., glutamate. When a presynaptic neuron contains more than one transmitter, however, potentiation can in principle be implemented by a transmitter different from that which elicits the EPSPs. Neuron B20 in Aplysia contains both dopamine and GABA. Although only dopamine acts as the fast excitatory transmitter at the B20-to-B8 synapse, GABA increases the size of these dopaminergic EPSPs. We now provide evidence that repeated stimulation of B20 potentiates B20-evoked dopaminergic EPSPs in B8 apparently via a postsynaptic mechanism, and short-term potentiation of this synapse is critical for the establishment and maintenance of an egestive network state. We show that GABA can act postsynaptically to increase dopamine currents that are elicited by direct applications of dopamine to B8 and that dopamine is acting on a 5-HT 3 -like receptor. This potentiation is mediated by GABA B -like receptors as GABA B -receptor agonists and antagonists, respectively, mimicked and blocked the potentiating actions of GABA. The postsynaptic actions of GABA rely on a G protein-mediated activation of PKC. Our results suggest that the postsynaptic action of cotransmitter-mediated potentiation may contribute to the maintenance of the egestive state of Aplysia feeding network and, in more general terms, may participate in the plasticity of networks that mediate complex behaviors.

Mechanisms and functions of GABA co-release

“…Co-expression of both vesicular transporters might allow for the presence of separate pools of vesicles enriched with each neurotransmitter. These observations support a large body of work in several species indicating that there is significant overlap in the expression of dopaminergic and GABAergic markers in the developing and mature nervous systems, under both physiological and pathological conditions [42][43][44][45] , which collectively suggest that GABA is a ubiquitous co-transmitter in dopaminergic neurons[AU: OK? ].…”

GABA‐like immunoreactivity in Biomphalaria: Colocalization with tyrosine hydroxylase‐like immunoreactivity in the feeding motor systems of panpulmonate snails

“…It was therefore proposed that these rapid EPSPs were mediated by dopamine. GABA, acting through GABAB‐like receptors and protein kinase C, was shown to modulate the rapid dopaminergic EPSPs in a target specific manner (Díaz‐Ríos & Miller, ; Svensson et al, ). The comprehensive understanding of the anatomy, physiology, and function of B20 and B65 provides a contextual framework for characterizing the GABA‐DA phenotype in panpulmonates.…”

“…In addition to their individual roles as gastropod neurotransmitters, evidence suggests that GABA and DA may co‐exist in specific neurons in the euopisthobranch gastropod Aplysia californica (Díaz‐Ríos et al, ). The colocalization of GABA and DA in five identified neurons within the feeding central pattern generator circuit of Aplysia enabled investigators to probe their respective contributions to synaptic signaling and specification of motor patterns in a multifunctional motor system (Due et al, ; Díaz‐Ríos & Miller, ; Svensson et al, ).…”

General Principles of Neuronal Co-transmission: Insights From Multiple Model Systems

“…GABA potentiated fast dopaminergic responses in B8 and the effect is blocked by the GABA B receptor antagonist phaclofen. Adapted from Koh et al (2003), Koh and Weiss (2005) and Svensson et al (2014).…”

“…Egestion is activated by repetitive stimulation of the esophageal nerve, which induces a short-term potentiation of synaptic transmission between interneuron B20 and the follower motor neuron B8. B20 co-localizes GABA and dopamine (Díaz-Ríos and Miller, 2005; Svensson et al, 2014). Dopamine acts as a fast-excitatory transmitter by acting on a 5-HT 3 -like receptor.…”