L&B Electrophysiology Services

L&B Electrophysiology Services

The development of effective, new therapeutics for the majority of CNS diseases is challenged by the neuronal diversity and connectivity of the brain. This level of complexity requires an understanding of organizational principles and cell-type specificity. Electrophysiology and functional connectomics are key tools in elucidating the mechanisms of action underlying the pathophysiology of CNS disorders and facilitating the development of new therapeutics. Accordingly, we support preclinical R&D programs in the areas of neurodegeneration, neurocognition and functional connectomics by providing electrophysiological characterization of small molecules with a focus on target engagement, efficacy and potency in acute rodent and human brain slices, cultured neurons and animal models.

In vitro slice physiology

human and rodent brain slices maintain functional local synaptic circuitry with a preserved brain architecture, while allowing precise control of the extracellular environment and drug pharmacology. We offer the measurement of neuronal excitability on a single cell-level to evaluate the effects of pharmacological agents on distinct neuronal cell types, receptors, ion channels or neurotransmitter systems. Whole cell recordings are tailored to the specific characteristics and mechanisms of action of the investigational substance. Specifically, we can offer multi-parameter functional analysis including:

Analysis of synaptic transmission

analysis of synaptic evoked and spontaneous synaptic currents/potentials, their biophysical properties, facilitation and depression, analysis of agonist/antagonist evoked postsynaptic current, analysis of input/output properties, evaluation of the function of feedback and feedforward inhibitory network motifs

  • analysis of firing properties (current clamp recording in slices)
  • comprehensive analysis of different voltage-gated current types, including their biophysical properties (voltage-clamp recordings in isolated neurons)

  • anticonvulsant drug pharmacology, pharmacosensitivity of voltage-dependent sodium channels, anticonvulsant activity on neuronal inhibition/excitation
  • evaluation of unwanted drug effects on basal neurotransmission and convulsive activity

  • chronic models of epilepsy (pilocarpine model, kainate model)
  • chronic stroke models (photothrombotic stroke)
  • models of cortical epilepsy

  • acutely dissociated dentate granule neurons
  • acutely dissociated CA1 neurons
  • transfected HEK293 and CHO cells
  • primary neuronal cultures

  • continuous telemetric EEG recordings in mice
  • patch-clamp and extracellular recordings in mice
  • behavioural testing

  • generation of RABV and rAAV virus constructs
  • stereotactic virus delivery
  • virus-mediated monosynaptic tracing from defined single neurons or neuronal populations
  • whole brain tissue clearing
  • image analysis and quantification of connected neurons
  • microscopic visualization of connectomes