Hippocampal Synaptic Plasticity
hippocampal synaptic plasticity
Disinhibitory and neuromodulatory regulation of hippocampal synaptic plasticity
The CA1 pyramidal neurons are embedded in an intricate local circuitry that contains a variety of interneurons. The roles these interneurons play in the regulation of the excitatory synaptic plasticity remains largely understudied. Recent experiments showed that repeated cholinergic activation of 𝛼7 nACh receptors expressed in oriens-lacunosum-moleculare (OLM𝛼2) interneurons could induce LTP in SC-CA1 synapses. We used a biophysically realistic computational model to examine mechanistically how cholinergic activation of OLMa2 interneurons increases SC to CA1 transmission. Our results suggest that, when properly timed, activation of OLMa2 interneurons cancels the feedforward inhibition onto CA1 pyramidal cells by inhibiting fast-spiking interneurons that synapse on the same dendritic compartment as the SC, i.e., by disinhibiting the pyramidal cell dendritic compartment. Our work further describes the pairing of disinhibition with SC stimulation as a general mechanism for the induction of synaptic plasticity. We found that locally-reduced GABA release (disinhibition) paired with SC stimulation could lead to increased NMDAR activation and intracellular calcium concentration sufficient to upregulate AMPAR permeability and potentiate the excitatory synapse. Our work suggests that inhibitory synapses critically modulate excitatory neurotransmission and induction of plasticity at excitatory synapses. Our work also shows how cholinergic action on OLM interneurons, a mechanism whose disruption is associated with memory impairment, can down-regulate the GABAergic signaling into CA1 pyramidal cells and facilitate potentiation of the SC-CA1 synapse.
Presynaptic plasticity in hippocampal circuits
Christophe Mulle is a cellular neurobiologist with expertise in electrophysiology of synaptic transmission and an international leader in studies on glutamate receptors and hippocampal synaptic plasticity. He was among the first to identify and characterize functional nicotinic receptors in the mammalian brain while working in the laboratory of Jean-Pierre Changeux at the Pasteur Institute. He then generated knock-out mice for KAR subunits at the Salk Institute in the laboratory of Steve Heinemann, which have proven to be instrumental for understanding the function of these elusive glutamate receptors in synaptic function and plasticity.
Investigating hippocampal synaptic plasticity in Schizophrenia: a computational and experimental approach using MEA recordings
Bernstein Conference 2024
Cannabidiol modulated compensation of radiation-induced alterations in hippocampal synaptic plasticity and neuronal function
FENS Forum 2024
Diurnal variations in the contribution of mGlu5 receptors to hippocampal synaptic plasticity
FENS Forum 2024
Exploring the impact of alpha-ketoglutarate on hippocampal synaptic plasticity in an Alzheimer's disease mouse model
FENS Forum 2024
Lifelong consumption of saturated and unsaturated fats induced the impairment of hippocampal synaptic plasticity and spatial learning and memory
FENS Forum 2024
TRESK potassium channel exerts a brake on neuronal excitability and modulates hippocampal synaptic plasticity
FENS Forum 2024