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CNS drug discovery

Brain slice electrophysiology

Understanding the effects of test compounds on brain slice tissue

Brain slices are valuable experimental tools which allow electrophysiological recordings from neurons within their functional environs in situ. In contrast to isolated and/or cultured brain cells, brain slices retain the anatomical architecture of the brain tissue and the synaptic circuitry within. This allows a more holistic understanding of the effects of pharmacological compounds on the entire tissue which may directly or indirectly affect neuronal ion channel function and excitatory activity.

By working with us you will have access to many years’ experience of manual patch-clamp recordings from a variety of brain regions.

We use electrophysiological protocols to study passive and active membrane properties, and to elucidate pharmacological and electrophysiological characteristics of neuronal currents and activity-dependent synaptic plasticity and transmission.

We offer:

  • Electrophysiological studies on acutely prepared rodent brain slices.
  • Variety of endpoints: Intrinsic firing properties, spontaneous and evoked responses.
  • Optimised perfusion system for pharmacological studies.
Representative data from rodent brain slices
Figure 1. Hippocampal spontaneous post-synaptic currents (sPSCs) and current-clamp recordings of action potential firing. A. Representative bright field image of a rodent hippocampus (left panel), with the subfields cornu ammonis 1 (CA1) and 3 (CA3), and dentate gyrus (DG) indicated. A representative neuron from CA1 (indicated within the box) is shown with a glass recording electrode attached during an experiment (right panel). B. A representative recording of spontaneous post-synaptic currents at -70 mV holding potential. The inset illustrates a zoomed-in area of the recording. C. Action potential responses to 1-second pulses of injected current as indicated in the current-clamp protocol (upper panel).
Pharmacological and electrophysiological characterisation of  hippocampal evoked post-synaptic currents
Figure 2. Pharmacological and electrophysiological characterisation of  hippocampal evoked post-synaptic currents.
A. Representative bright field image of a rodent hippocampus (left panel), with the subfields cornu ammonis 1 (CA1) and 3 (CA3), and dentate gyrus (DG) indicated. A stimulating electrode was attached close to CA1, as illustrated.
B. A representative recordings of evoked post-synaptic currents from hippocampal neurons from CA1, utilising ‘paired-pulse’ stimulation to investigate synaptic plasticity. The effect of reducing the inter-stimulus interval from 500 (i) to 100 (ii) ms illustrates synaptic facilitation, whereby the amplitude of the second evoked current is enhanced as illustrated by the dashed arrow in panel ii.
C. Representative recordings of evoked post-synaptic currents illustrating the different components which make up evoked post-synaptic currents. Recordings were performed after exposure to the NMDA receptor inhibitor D (-)-2-amino-5-phosphonvalerate (DAPV), both alone and in combination with the AMPA receptor inhibitor 2,3-dioxo-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), and GABA antagonist, gabazine. D. A representative current-time plot showing the peak inward and outward currents recorded from the different components of the evoked post-synaptic currents during a 15-minute recording.

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