Sympathetic nerve activity and blood pressure increases elicited by phototimulation of Channelrhodopsin-2 expressing ventral medullary astrocytes.

University of Manchester (2010) Proc Physiol Soc 19, C77

Oral Communications: Sympathetic nerve activity and blood pressure increases elicited by phototimulation of Channelrhodopsin-2 expressing ventral medullary astrocytes.

N. Marina1, M. Figueiredo2, A. G. Teschemacher2, S. Kasparov2, A. Gourine1

1. Neuroscience, Physiology and Pharmacology, UCL, London, United Kingdom. 2. Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.

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Astrocytes have always been considered to provide structural and metabolic support to neurons. However, recent studies have shown that astrocytes are also capable of regulating synaptic strength and information processing and therefore might play an important role in the regulation of complex central nervous functions (Allen & Barres, 2009). In this study, we selectively activated ventral medullary astrocytes in vivo using adenoviral vector-driven transgene expression to explore their role in the regulation of central sympathetic tone and blood pressure (BP). Male Wistar rats were anaesthetised with a mixture of ketamine (60 mg/kg, i.m.) and medetomidine (250 μg/kg, i.m.) and received bilateral microinjections in the rostral ventrolateral medulla (RVLM) of AVV-sGFAP-ChR2(H134R)-Katushka1.3, an adenovirus that expresses channelrhodopsin-2 (ChR2) H134R mutant under the control of the enhanced astrocytic-specific promoter GFAP (Liu et al., 2008). The wound was sutured and anesthesia was reversed with atipemazole (1 mg/kg) and post-operative care was taken. Animals were re-anaesthetised 7-14 days after the injections with pentobarbitone (60 mg/kg i.p.) and the ventral medullary surface was exposed as described previously (Gourine et al., 2005). Mean arterial blood pressure (MABP) and renal nerve sympathetic discharge (SND) were monitored. RESULTS. Unilateral stimulation of ChR2-transduced ventral medullary astrocytes with blue light (445 nm wavelength; ~15 mW, 20/20 ms duty cycle for 20 seconds) increased MABP (+20.7 mmHg, n=11) and SND (+28.7 %, n=11). MABP and SND remained elevated during the period of stimulation and then gradually recovered (5 – 10 min). Similar responses were easily obtained with subsequent photostimulations. Immunohistochemical analysis revealed Strong ChR2-Katushka1.3 expression in ventral medullary astrocytes that were in close proximity to tyrosine hydroxilase-immunoreactive neurones within the RVLM. CONCLUSIONS: Activation of ventral medullary astrocytes elicits significant sympathoexcitation and rise in blood pressure. This is the first evidence that astroglia may play a role in the regulation of the central sympathetic control.



Where applicable, experiments conform with Society ethical requirements.

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