Abstract
Here we demonstrate that cerebellar stellate cells diffusionally isolate synaptically evoked signals in dendrites and are capable of input-specific synaptic plasticity. Sustained activity of parallel fibers induces a form of long-term depression that requires opening of calcium (Ca(2+))-permeable AMPA-type glutamate receptors (CP-AMPARs) and signaling through class 1 metabotropic glutamate receptors (mGluR1) and CB1 receptors. This depression is induced by postsynaptic increases in Ca(2+) concentration ([Ca(2+)]) and is limited to activated synapses. To understand how synapse-specific plasticity is induced by diffusible second messengers in aspiny dendrites, we examined diffusion of Ca(2+) and small molecules within stellate cell dendrites. Activation of a single parallel fiber opened CP-AMPARs, generating long-lived Ca(2+) transients that were confined to submicron dendritic stretches. The diffusion of Ca(2+) was severely retarded due to interactions with parvalbumin and a general restriction of small molecule mobility. Thus stellate cell dendrites spatially restrict signaling cascades that lead from CP-AMPAR activation to endocannabinoid production and trigger the selective regulation of active synapses.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Calcium / metabolism
-
Calcium Channels / drug effects
-
Calcium Channels / metabolism
-
Calcium Signaling / drug effects
-
Calcium Signaling / physiology
-
Cell Compartmentation / physiology
-
Cerebellar Cortex / cytology
-
Cerebellar Cortex / drug effects
-
Cerebellar Cortex / physiology*
-
Dendrites / drug effects
-
Dendrites / physiology*
-
Electric Stimulation
-
Excitatory Amino Acid Antagonists / pharmacology
-
Interneurons / drug effects
-
Interneurons / physiology*
-
Long-Term Synaptic Depression / drug effects
-
Long-Term Synaptic Depression / physiology
-
Neuronal Plasticity / physiology*
-
Organ Culture Techniques
-
Parvalbumins / metabolism
-
Patch-Clamp Techniques
-
Rats
-
Receptor, Cannabinoid, CB1 / drug effects
-
Receptor, Cannabinoid, CB1 / metabolism
-
Receptors, AMPA / drug effects
-
Receptors, AMPA / metabolism
-
Receptors, Metabotropic Glutamate / drug effects
-
Receptors, Metabotropic Glutamate / metabolism
-
Signal Transduction / drug effects
-
Signal Transduction / physiology
-
Synapses / drug effects
-
Synapses / physiology*
-
Synaptic Membranes / drug effects
-
Synaptic Membranes / metabolism
-
Synaptic Transmission / physiology*
Substances
-
Calcium Channels
-
Excitatory Amino Acid Antagonists
-
Parvalbumins
-
Receptor, Cannabinoid, CB1
-
Receptors, AMPA
-
Receptors, Metabotropic Glutamate
-
metabotropic glutamate receptor type 1
-
Calcium