Dataset Information

MGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.

ABSTRACT: Excitatory and inhibitory transmission onto lateral habenula (LHb) neurons is instrumental for the expression of positive and negative motivational states. However, insights into the molecular mechanisms modulating synaptic transmission and the repercussions for neuronal activity within the LHb remain elusive. Here, we report that, in mice, activation of group I metabotropic glutamate receptors triggers long-term depression at excitatory (eLTD) and inhibitory (iLTD) synapses in the LHb. mGluR-eLTD and iLTD rely on mGluR1 and PKC signaling. However, mGluR-dependent adaptations of excitatory and inhibitory synaptic transmission differ in their expression mechanisms. mGluR-eLTD occurs via an endocannabinoid receptor-dependent decrease in glutamate release. Conversely, mGluR-iLTD occurs postsynaptically through PKC-dependent reduction of ?2-containing GABAA-R function. Finally, mGluR-dependent plasticity of excitation or inhibition decides the direction of neuronal firing, providing a synaptic mechanism to bidirectionally control LHb output. We propose mGluR-LTD as a cellular substrate that underlies LHb-dependent encoding of opposing motivational states.

SUBMITTER: Valentinova K

PROVIDER: S-EPMC5009114 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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mGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.

Valentinova Kristina K Mameli Manuel M

Cell reports 20160818 9

Excitatory and inhibitory transmission onto lateral habenula (LHb) neurons is instrumental for the expression of positive and negative motivational states. However, insights into the molecular mechanisms modulating synaptic transmission and the repercussions for neuronal activity within the LHb remain elusive. Here, we report that, in mice, activation of group I metabotropic glutamate receptors triggers long-term depression at excitatory (eLTD) and inhibitory (iLTD) synapses in the LHb. mGluR-eL ...[more]

PMID: 27545888

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Project description:A key feature of excitatory synapses is the existence of subsynaptic protein nanoclusters whose precise alignment across the cleft in a trans-synaptic nanocolumn influences the strength of synaptic transmission. However, whether nanocolumn properties vary between excitatory synapses functioning in different cellular contexts is unknown. We used a combination of confocal and DNA-PAINT super-resolution microscopy to directly compare the organization of shared scaffold proteins at two important excitatory synapses - those forming onto excitatory principal neurons (Ex→Ex synapses) and those forming onto parvalbumin-expressing interneurons (Ex→PV synapses). As in Ex→Ex synapses, we find that in Ex→PV synapses presynaptic Munc13-1 and postsynaptic PSD-95 both form nanoclusters that demonstrate alignment, underscoring synaptic nanostructure and the trans-synaptic nanocolumn as conserved organizational principles of excitatory synapses. Despite the general conservation of these features, we observed specific differences in the characteristics of pre- and postsynaptic Ex→PV nanostructure. Ex→PV synapses contained larger PSDs with fewer PSD-95 NCs when accounting for size than Ex→Ex synapses. Furthermore, the PSD-95 NCs were larger and denser. The identity of the postsynaptic cell also had a retrograde impact on Munc13-1 organization, as Ex→PV synapses hosted larger Munc13-1 puncta that contained less dense but larger and more numerous Munc13-1 NCs. Moreover, we measured the spatial variability of transsynaptic alignment in these synapse types, revealing protein alignment in Ex→PV synapses over a distinct range of distances compared to Ex→Ex synapses. We conclude that while general principles of nanostructure and alignment are shared, cell-specific elements of nanodomain organization likely contribute to functional diversity of excitatory synapses. Understanding the rules of synapse nanodomain assembly, which themselves are cell-type specific, will be essential for illuminating brain network dynamics.

Dataset Information

MGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.

Publications

mGluR-LTD at Excitatory and Inhibitory Synapses in the Lateral Habenula Tunes Neuronal Output.

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