When it comes to understanding how the brain - or any neural system - truly functions, studying its native environment is essential. Electrophysiology in live tissue preparations preserves the spatial and functional integrity of real neural circuits, allowing researchers to observe electrical activity as it occurs in the living systems. This approach offers an accurate, nuanced view of neuronal communication - one that brings us closer to decoding how the brain truly works.

Figure 1: MEA Activity in a Brain Slice

Electrophysiology in Native Tissue Landscapes

Traditional in vitro cellular models often strip away the complexity of the neuronal environment. In contrast, native tissue preparations, such as brain slices, preserve the structural and functional integrity of neural circuits, making them a powerful platform for: 

  • Physiological Integrity: Native tissue captures the complexity of the intact system, providing an accurate reflection of how neurons behave in their original environment.
  • Network-Level Dynamics: It retains synaptic connectivity and structural layout of neuronal circuits, allowing the study of dynamic interactions as they naturally occur.
  • Translational Value: By preserving the complexity of living systems, native tissue improves the relevance of preclinical data for therapeutic development.
  • Minimized Artifacts: Unlike artificial systems, native tissue maintains natural protein expression and cellular relationships, reducing the risk of misleading results.

Evotec’s Platforms for Electrophysiology in Native Models

Native tissue electrophysiology offers a powerful platform to accelerate translational research and shape the future of therapeutic development: 

  • Manual Patch Clamp: For precise recordings from individual neurons or cells within intact tissue.
  • Field Recordings: Ideal for assessing population-level activity and modifications in synaptic transmission, including phenomena such as long-term potentiation (LTP) and long-term depression (LTD), which underlie cognitive processes like memory. It also allows the assessment of seizure-like activity as an indicator of potential convulsive effects for safety side effects.
  • Multi-Electrode Arrays (MEAs): Captures spatiotemporal patterns of activity across tissue regions in healthy and disease models.
  • Wire Myograph: Measures contractility in smooth muscle tissue rings or vessels, particularly valuable in respiratory and cardiovascular fields.
  • Ussing Chambers: Quantifies ion transport across epithelial membranes, supporting studies in respiratory and gut physiology.

Applications Across Research Areas

Native tissue models are increasingly used to bridge basic research and translational applications:

  • Neurodegeneration: Studying synaptic loss and circuit dysfunction e.g. in Alzheimer’s, Parkinson’s or ALS models.
  • Epilepsy: Investigating seizure propagation and network excitability and testing anticonvulsants.
  • Pain Pathways: Exploring spinal cord and peripheral tissue responses.
  • Psychiatric Research: Understanding altered connectivity and neurotransmission in models of depression and schizophrenia.
  • Sleep Disorders: Investigating mechanisms and therapeutic approaches for conditions such as narcolepsy and sleep-related breathing disorders, including sleep apnea.

And extending into other key therapeutic areas:

  • Respiratory Diseases
  • Cardiac Health
  • Reproductive Health
  • Gut Health
  • Immunological Diseases
  • Cancer

These applications are supported by a wide range of native tissue models, including brain slices, peripheral nerves, smooth muscle tissue, airway epithelium and cardiac tissue - each offering unique insights into disease mechanisms and therapeutic responses.

Accelerating Drug discovery and Preclinical Innovation 

Native tissue electrophysiology is advancing preclinical research by providing physiologically grounded insights that reflect the complexity of living system. With advanced platforms and diverse tissue models, this approach empowers researchers to explore complex biological systems across a wide range of therapeutic areas - from neurodegeneration and pain to cardiac health, respiratory diseases and beyond. As we move toward more predictive and translational science, native tissue is proving to be a vital tool in accelerating drug discovery and shaping the future of biomedical innovation.

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