Scientists present methodology and research findings from neurophysiological studies in head-fixed, behaving mice.

euroscience research in freely behaving animals is inherently challenging for techniques that require a high degree of precision, such as 2-photon imaging, single-cell optogenetics and patch clamp recording. Scientists are forced to use general anesthesia to immobilize animals for single-cell recording and microscopy. Unfortunately, anesthetics have a profound physiological impact that compromises data quality and translational relevance.

In this webinar sponsored by Neurotar, experts present their research utilizing the Mobile HomeCage®, an experimental tool which ensures the stability required for high-precision neurophysiological techniques while allowing mice to navigate and explore their environment.

Case Study #1:
Dr. Sarah Stuart and Dr. Jon Palacios-Filardo of the University of Bristol present their studies combining analysis of goal-directed behavior with whole-cell recordings from the hippocampus of awake mice. The researchers share useful tips for the surgery protocol and for adjusting the head fixation angle in order to facilitate mouse motility and exploratory behavior.

Case Study #2:
Dr. Alexander Dityatev and Weilun Sun from the German Center for Neurodegenerative Diseases (DZNE) discuss 2-photon imaging of fluorescently labeled microglia in vivo in the context of neurodegenerative disease. They also present their recent data on the effects of different anesthetics on the microglial response to localized laser injury.

Case Study #3:
Dr. Norbert Hájos from the Hungarian Academy of Sciences presents his lab’s research into the amygdala’s role in reward-driven behavior. He shares the challenges of making single-unit recordings using silicon probes during mouse locomotion and subsequent morphological identification of active neurons in the amygdala.

Key Topics Include:

  • Requirements for stable single-cell recordings and 2-photon imaging in behaving mice
  • Challenges of combining high-precision techniques with behavioral research
  • Methodological considerations for improving exploratory behavior in head-fixed mice
  • Quantitative analysis of microglial function using 2-photon microscopy in awake mice
  • Recording neuronal activity in the amygdala of awake mice followed by morphological identification of recorded neurons

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Resources

Presenters

Research Associate
School of Physiology, Pharmacology & Neuroscience
University of Bristol

Sarah is a member of the Jack Mellor lab at University of Bristol. Memory is fundamentally dependent on the behavioural context of learnt information and we aim to investigate the contextual factors that are important for the encoding of memory by synaptic plasticity at a neuronal circuit level. We study this by considering the factors that regulate the induction of synaptic plasticity and the mechanisms underlying its expression. Currently this involves projects in the following areas: The role of acetylcholine and other neuromodulators in synaptic circuit function; the patterns of activity that induce synaptic plasticity; and the mechanisms underlying postsynaptic neurotransmitter receptor trafficking. We use a combination of techniques including in vitro and in vivo electrophysiology, 2-photon imaging, optogenetics, behavioural assays and computational modelling.


School of Physiology, Pharmacology & Neuroscience
University of Bristol

Our ability to learn and remember information about our environment is underpinned by synaptic plasticity. This process is fundamental to shaping who we are as individuals and is also implicated in many neurological and psychiatric disorders. Memory is fundamentally dependent on the behavioural context of learnt information and we aim to investigate the contextual factors that are important for the encoding of memory by synaptic plasticity at a neuronal circuit level.

Molecular Neuroplasticity
DZNE – German Center for Neurodegenerative Diseases

Since 2012 Alexander Dityatev is the head of the Molecular Neuroplasticity research group at DZNE and a full professor at the University of Magdeburg. His group is studying the role of extracellular matrix (ECM) molecules in major brain diseases and develops new strategies to image and target the ECM. The group combines expertise in vitro and in vivo electrophysiology, in vivo two-photon imaging and molecular biology.

PhD Student
DZNE – German Center for Neurodegenerative Diseases

Our studies demonstrate that attenuation of the neural ECM, particularly in the form of hyaluronic acid and chondroitin sulfate-rich perineuronal nets, is found in the ketamine model of schizophrenia and may result in epileptiform activity. The mechanisms underlying ECM attenuation involve an upregulation of the activities of matrix metalloproteinases, such as ADAMTS4/5 and MMP-9. They appeared to be under the control of dopaminergic and serotoninergic systems, involving D1-like and 5-HT7 receptors, respectively. Our pioneering works revealed the role of ECM in synaptic plasticity. For example, tenascin-C supports induction of long-term potentiation (LTP) at CA3-CA1 synapses and the extinction of fear memories by regulation of L-type voltage-gated Ca2+ channels. Similarly, hyaluronic acid regulates synaptic plasticity through these channels. Another mechanism involves a control of axonal excitability by heparan sulfates. In vivo, heparinase treatment impairs context discrimination in a fear conditioning paradigm and oscillatory network activity in the low theta frequency band.

Group Leader
Institute of Experimental Medicine
Hungarian Academy of Sciences

Norbert Hájos is the Group Leader of the Network Neurophysiology Laboratory at the Institute of Experimental Medicine, HAS. The lab is most interested in the cellular and synaptic mechanisms underlying the neuronal network operation in the cortical areas. Our main goal is to uncover the principles of information processing in cortical microcircuits at cellular and network levels. To this end, we examine the features of the connections among neurons using neuroanatomy, electrophysiology, imaging techniques and optogenetic approaches.

Production Partner

Neurotar

Neurotar develops instrumentation for microscopic imaging and electrophysiological recordings in the brain of awake head-fixed mice. Its proprietary Mobile HomeCage® allows integrating high-precision tests with behavior, starting from simple locomotion tracking to maze navigation. Neurotar has extensive imaging experience: the company pioneered in vivo two-photon imaging as contract research for the pharmaceutical industry in 2010. It has since extended its service portfolio to imaging studies in awake behaving mice.

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