Neuronal
neuronal excitability
Glycolysis regulates neuronal excitability via lactate receptor, HCA1R
Redox and mitochondrial dysregulation in epilepsy
Epileptic seizures render the brain uniquely dependent on energy producing pathways. Studies in our laboratory have been focused on the role of redox processes and mitochondria in the context of abnormal neuronal excitability associated with epilepsy. We have shown that that status epilepticus (SE) alters mitochondrial and cellular redox status, energetics and function and conversely, that reactive oxygen species and resultant dysfunction can lead to chronic epilepsy. Oxidative stress and neuroinflammatory pathways have considerable crosstalk and targeting redox processes has recently been shown to control neuroinflammation and excitability. Understanding the role of metabolic and redox processes can enable the development of novel therapeutics to control epilepsy and/or its comorbidities.
How does the metabolically-expensive mammalian brain adapt to food scarcity?
Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. I addressed this in the visual cortex of awake mice using whole-cell recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. I found that food restriction reduced synaptic ATP usage by 29% through a decrease in AMPA receptor conductance. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in orientation tuning and impaired fine visual discrimination. This reduction in coding precision was associated with reduced levels of the fat mass-regulated hormone leptin and was restored by exogenous leptin supplementation. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.
Neocortex saves energy by reducing coding precision during food scarcity
Information processing is energetically expensive. In the mammalian brain, it is unclear how information coding and energy usage are regulated during food scarcity. We addressed this in the visual cortex of awake mice using whole-cell patch clamp recordings and two-photon imaging to monitor layer 2/3 neuronal activity and ATP usage. We found that food restriction resulted in energy savings through a decrease in AMPA receptor conductance, reducing synaptic ATP usage by 29%. Neuronal excitability was nonetheless preserved by a compensatory increase in input resistance and a depolarized resting membrane potential. Consequently, neurons spiked at similar rates as controls, but spent less ATP on underlying excitatory currents. This energy-saving strategy had a cost since it amplified the variability of visually-evoked subthreshold responses, leading to a 32% broadening in orientation tuning and impaired fine visual discrimination. These findings reveal novel mechanisms that dynamically regulate energy usage and coding precision in neocortex.
Capacitance clamp - artificial capacitance in biological neurons via dynamic clamp
A basic time scale in neural dynamics from single cells to the network level is the membrane time constant - set by a neuron’s input resistance and its capacitance. Interestingly, the membrane capacitance appears to be more dynamic than previously assumed with implications for neural function and pathology. Indeed, altered membrane capacitance has been observed in reaction to physiological changes like neural swelling, but also in ageing and Alzheimer's disease. Importantly, according to theory, even small changes of the capacitance can affect neuronal signal processing, e.g. increase network synchronization or facilitate transmission of high frequencies. In experiment, robust methods to modify the capacitance of a neuron have been missing. Here, we present the capacitance clamp - an electrophysiological method for capacitance control based on an unconventional application of the dynamic clamp. In its original form, dynamic clamp mimics additional synaptic or ionic conductances by injecting their respective currents. Whereas a conductance directly governs a current, the membrane capacitance determines how fast the voltage responds to a current. Accordingly, capacitance clamp mimics an altered capacitance by injecting a dynamic current that slows down or speeds up the voltage response (Fig 1 A). For the required dynamic current, the experimenter only has to specify the original cell and the desired target capacitance. In particular, capacitance clamp requires no detailed model of present conductances and thus can be applied in every excitable cell. To validate the capacitance clamp, we performed numerical simulations of the protocol and applied it to modify the capacitance of cultured neurons. First, we simulated capacitance clamp in conductance based neuron models and analysed impedance and firing frequency to verify the altered capacitance. Second, in dentate gyrus granule cells from rats, we could reliably control the capacitance in a range of 75 to 200% of the original capacitance and observed pronounced changes in the shape of the action potentials: increasing the capacitance reduced after-hyperpolarization amplitudes and slowed down repolarization. To conclude, we present a novel tool for electrophysiology: the capacitance clamp provides reliable control over the capacitance of a neuron and thereby opens a new way to study the temporal dynamics of excitable cells.
Altered excitatory/inhibitory balance in the prefrontal cortex of the IB2 KO mouse model of autism: From neuronal excitability to cerebellar modulation in vivo
FENS Forum 2024
Astrocyte activity triggers adaptive myelin plasticity and increased neuronal excitability in the somatosensory cortex following sensory deprivation
FENS Forum 2024
Cell-type specific actions of Nogo-A in controlling spatial memory formation by modulating neuronal excitability
FENS Forum 2024
Dual effect of anandamide and its endogenous precursor 20:4-NAPE on DRG neuronal excitability and nociception
FENS Forum 2024
So excited to see you! Visual object-in-place learning increases neuronal excitability in lateral entorhinal cortex engram cells
FENS Forum 2024
Nogo-A regulates fear memory processes and memory engram formation by modulating neuronal excitability in a sex-specific manner
FENS Forum 2024
Role of the CaSR in neuronal excitability in CA1 hippocampal region
FENS Forum 2024
Temporal dynamics of neuronal excitability in the lateral amygdala mediates allocation to an engram supporting conditioned fear memory
FENS Forum 2024
TRESK potassium channel exerts a brake on neuronal excitability and modulates hippocampal synaptic plasticity
FENS Forum 2024
Visual activity enhances neuronal excitability in thalamic relay neurons
FENS Forum 2024