Synapse Number and Synaptic Efficacy Are Regulated by Presynaptic cAMP and Protein Kinase A

Abstract

The mechanisms by which neurons regulate the number and strength of synapses during development and synaptic plasticity have not yet been defined fully. This lack of fundamental knowledge in the fields of neurodevelopment and synaptic plasticity can be attributed, in part, to compensatory mechanisms by which neurons accommodate for the loss of function in their synaptic partners. This is generally achieved either by scaling up neuronal transmitter release capabilities or by enhancing the postsynaptic responsiveness. Here, we demonstrate that regulation of synaptic strength and number between identified Lymnaea neurons visceral dorsal 4 (VD4, the presynaptic cell) and left pedal dorsal 1 (LPeD1, the postsynaptic cell) requires presynaptic activation of a cAMP-PKA-dependent signal. Experimental activation of the cAMP-PKA pathway resulted in reduced synaptic efficacy, whereas inhibition of the cAMP-PKA cascade permitted hyperinnervation and an overall enhancement of synaptic strength. Because synaptic transmission between VD4 and LPeD1 does not require a cAMP-PKA pathway, our data show that these messengers may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity.

Lidocaine treatment during synapse reformation periods permanently inhibits NGF-induced excitation in an identified reconstructed synapse of Lymnaea stagnalis

“…Our results demonstrate that lidocaine exposure during synapse reformation periods is able to suppress NGF-induced MEPPs permanently. Neurotrophic factors, such as NGF, have been reported to act as protein kinase A (PKA) because the inhibitor for PKA was able to inhibit synapse reformation within 24 h. In other words, these messengers of cyclic adenosine monophosphate (cAMP)-PKA pathway may play a novel role in regulating the synaptic efficacy during early synaptogenesis and plasticity induced by neurotrophic factors [27].…”

Cloning and Characterization of a P2X Receptor Expressed in the Central Nervous System of Lymnaea stagnalis

“…One potential strategy which could be of use in gaining a better understanding of these roles could be to study P2X receptor function in the CNS of a simple model organism. The pond snail Lymnaea stagnalis has a relatively simple CNS containing ∼20,000 readily identifiable neurons [23] and has historically proved to be an extremely useful and accessible model to study fundamental aspects of CNS function such as synaptic plasticity [24] and associative memory [25]. Furthermore, the neuronal pathways underlying complex physiological processes such as feeding and respiration have been elucidated in this organism [26]–[28], making it an attractive model for investigating neural networks.…”

High-fidelity patch-clamp recordings from neurons cultured on a polymer microchip

“…We report the first recording of action potentials from neurons cultured on a polymer planar patch-clamp device. Having established the functionality of this micro-chip for patch-clamp recordings from neurons cultured on-chip, future work will focus on simultaneous recordings from neurons that are synaptically connected (Munno et al 2003, Smit et al 2001, Woodin et al 2002. This will allow us to examine neuronal communication and patterns of synaptic plasticity with a resolution not yet attained on a planar patch-clamp device.…”