Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

Abstract

Competition among different axons to reach the somatodendritic region of the target neuron is an important event during development to achieve the final architecture typical of the mature brain. Trasmitter-receptor matching is a critical step for the signaling between neurons. In the cerebellar cortex, there is a persistent competition between the two glutamatergic inputs, the parallel fibers and the climbing fibers, for the innervation of the Purkinje cells. The activity of the latter input is necessary to maintain its own synaptic contacts on the proximal dendritic domain and to confine the parallel fibers in the distal one. Here, we show that climbing fiber activity also limits the distribution of the GABAergic input in the proximal domain. In addition, blocking the activity by tetrodotoxin infusion in Wistar rat cerebellum, a synapse made by GABAergic terminals onto the recently formed Purkinje cell spines appear in the proximal dendrites. The density of GABAergic terminals is increased, and unexpected double symmetric/asymmetric postsynaptic densities add to the typical symmetric phenotype of the GABAergic shaft synapses. Moreover, glutamate receptors appear in these ectopic synapses even in the absence of glutamate transmitter inside the presynaptic terminal and close to GABA receptors. These results suggest that the Purkinje cell has an intrinsic tendency to develop postsynaptic assemblies of excitatory types, including glutamate receptors, over the entire dendritic territory. GABA receptors are induced in these assemblies when contacted by GABAergic terminals, thus leading to the formation of hybrid synapses.cerebellum ͉ GABA receptor ͉ spinogenesis ͉ synaptic plasticity

GluRδ2 Expression in the Mature Cerebellum of Hotfoot Mice Promotes Parallel Fiber Synaptogenesis and Axonal Competition

“…7D,E,G ). Recently, it has been shown that following blockage of electrical activity, GluRδ2 is expressed not only on spines but also in excitatory postsynaptic assemblies in the smooth surface of PC proximal dendrites [35]. In our experiments, we failed to observe GluRδ2 signals in the deeper section of the granular layer.…”

Activity-dependent neurotransmitter respecification

“…Activity ensures formation of functional synapses, and the level of activity determines the class of synapse. This process seems to involve the action of diffusible factors that may include the transmitters as well as other components, such as trophic factors 54–57 . The results are consistent with the demonstration of glutamatergic synapses by classically cholinergic neonatal mouse motor neurons 24,25 .…”

Reserve pool neuron transmitter respecification: Novel neuroplasticity

“…Transmitter receptor matching occurs in parallel with activity-dependent transmitter respecification (Borodinsky and Spitzer, 2007; Cesa et al, 2008; Dulcis and Spitzer, 2008). Transmitter and receptor respecification can be triggered by experimental manipulations or by natural sensory stimuli that selectively activate a neuronal circuit (Trudeau and Gutierrez, 2007; Dulcis and Spitzer, 2008).…”