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Dr Anja Teschemacher

Communication between Glia Cells and Neurones

Astrocytes, the most abundant type of glia cell in the brain, are much more than brain’glue’: Apart from giving structural and metabolic support to neurones, they actively participate in information processing on multiple levels.

We are particularly interested in the special relationship between astrocytes and noradrenergic neurones which constitute a major modulatory system that regulates fundamental brain states and vital functions, such as wakefuleness, attention to important stimuli, motivation, cardiovascular and respiratory activity.

The major questions our lab is currently focussing on are:

  • How does astroglial activity link to release of noradrenaline, and vice versa?
  • Which intracellular second messenger pathways are responsible for modulating release of the relevant glio- and neurotransmitters?
  • What are the physiological consequences of release, for example, for central control of blood pressure, cortical EEG, and behaviour?

We are addressing these questions by using a combination of electrophysiological (patch clamp; amperometry; fast scan cyclic voltammetry), optical (confocal imaging of living brain slice cultures; cell-specific optogenetic stimulation), molecular (viral gene transfer) and pharmacological tools.

Research keywords

  • Astrocytes
  • lactate
  • noradrenaline
  • locus coeruleus
  • cyclic AMP
  • viral vectors
  • optogenetics

Diseases related to this field of research

  • Hypertension
  • glioblastoma
  • Neurodegeneration

Processes and functions relevant to this work

  • Blood pressure homeostasis
  • blood pressure control
  • brainstem control mechanisms
  • neuroprotection

Equipment relevant to this work

  • Molecular biology equipment and apparatus
  • viral vector production facility
  • electrophysiology equipment
  • amperometric apparatus
  • confocal microscope
  • telemetry

Research findings

Astrocytes and Noradrenergic Neurones Communicate via L-lactate

Noradrenergic and adrenergic transmission in the brain plays roles in a number of vital physiological processes, including regulation of cardiovascular performance, mood, sleep-wake cycles and processing of pain information. Thus, dysfunction of central noradrenaline release may contribute to a number of major medical problems such as pathologically elevated blood pressure (essential hypertension), attention deficit-related disorders, depression or migraine.

We discovered that astrocytes signal via release of lactic acid to noradrenergic neurones, and thereby boost noradrenaline release. Very little is currently known about the intracellular and metabolic signalling that regulates these processes, nor about the receptors that mediate L-lactate actions in the brain.

We have developed a range of phenotype-selective viral vectors to specifically manipulate the activity of astrocytes and/or noradrenergic neurones and thus probe into their functions and roles within neural networks. This allows us to use optogenetic tools to activate the system, metabolic interference to depress it, and biosensors to monitor concurrent signalling. With the help of RNA sequencing and structure-activity approaches, we are in the process of characterising novel L-lactate receptor candidates.

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Collaborations

  • Sergey Kasparov - Bristol
  • David Jane - Bristol