Heterogeneous CaMKII-Dependent Synaptic Compensations in CA1 Pyramidal Neurons From Acute Hippocampal Slices.
Pablo Vergara1, Gabriela Pino1, Jorge Vera1
1Cell Physiology Center, Department of Biology, Faculty of Sciences, University of Chile, Santiago, Chile.
Frontiers in Cellular Neuroscience
|April 18, 2022
Summary
Deafferentation rapidly triggers homeostatic synaptic plasticity (HSP) in hippocampal neurons, involving AMPA receptor changes and CaMKII activation. These adaptations resemble slower forms of inactivity response, aiding understanding of brain injury recovery.
Area of Science:
- Neuroscience
- Synaptic Plasticity
- Molecular Biology
Background:
- Homeostatic synaptic plasticity (HSP) maintains neuronal network function during prolonged activity changes.
- Deafferentation, or loss of sensory input, can induce reactive functional changes potentially sharing mechanisms with HSP.
- Acute hippocampal slices offer a model to study rapid (hours) denervation-induced modifications.
Purpose of the Study:
- To investigate rapid synaptic modifications in CA1 pyramidal neurons following deafferentation in acute hippocampal slices.
- To explore the underlying molecular mechanisms, particularly the role of Ca2+/calmodulin-dependent kinase II (CaMKII).
Main Methods:
- Whole-cell recordings of miniature excitatory postsynaptic currents (mEPSCs) in CA1 pyramidal neurons over 12 hours post-slicing.
- Dissection of CA3 to isolate Schaffer collateral input.
- Analysis of mEPSC amplitude, decay time, and rise time to infer synapse location and receptor dynamics.
- Pharmacological inhibition of CaMKII.
Main Results:
- Observed increased mEPSC amplitude and decreased decay time, indicating AMPA receptor upregulation and subunit changes.
- Identified amplitude increases at specific dendritic domains, correlated with synapse location.
- Detected specific frequency increases in the same domains, alongside a global increase, with lower increments at initially active sites.
- CaMKII inhibition blocked or occluded amplitude and frequency upregulation.
Conclusions:
- Deafferentation rapidly induces diverse homeostatic compensations in hippocampal synapses, resembling known CaMKII-dependent HSP processes.
- These rapid adaptations suggest a role for CaMKII in fast-developing homeostatic or pathological events following brain injury.
- The findings highlight the brain's capacity for swift functional adjustments to sensory input loss.
