Activity-induced tissue oxygenation changes in rat cerebellar cortex: interplay of postsynaptic activation and blood flow

Authors

  • Nikolas Offenhauser,

    1. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
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  • Kirsten Thomsen,

    1. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
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  • Kirsten Caesar,

    1. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
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  • Martin Lauritzen

    1. Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
    2. Department of Clinical Neurophysiology, Glostrup Hospital, 2600 Glostrup, Denmark
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Corresponding author N. Offenhauser: University of Copenhagen, Department of Medical Physiology, The Panum Institute 12.5, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. Email: nikolas@offenhauser.de

Abstract

Functional neuroimaging relies on the robust coupling between neuronal activity, metabolism and cerebral blood flow (CBF), but the physiological basis of the neuroimaging signals is still poorly understood. We examined the mechanisms of activity-dependent changes in tissue oxygenation in relation to variations in CBF responses and postsynaptic activity in rat cerebellar cortex. To increase synaptic activity we stimulated the monosynaptic, glutamatergic climbing fibres that excite Purkinje cells via AMPA receptors. We used local field potentials to indicate synaptic activity, and recorded tissue oxygen partial pressure (Ptiss,O2) by polarographic microelectrodes, and CBF using laser-Doppler flowmetry. The disappearance rate of oxygen in the tissue increased linearly with synaptic activity. This indicated that, without a threshold, oxygen consumption increased as a linear function of synaptic activity. The reduction in Ptiss,O2 preceded the rise in CBF. The time integral (area) of the negative Ptiss,O2 response increased non-linearly showing saturation at high levels of synaptic activity, concomitant with a steep rise in CBF. This was accompanied by a positive change in Ptiss,O2. Neuronal nitric oxide synthase inhibition enhanced the initial negative Ptiss,O2 response (‘dip’), while attenuating the evoked CBF increase and positive Ptiss,O2 response equally. This indicates that increases in CBF counteract activity-induced reductions in Ptiss,O2, and suggests the presence of a tissue oxygen reserve. The changes in Ptiss,O2 and CBF were strongly attenuated by AMPA receptor blockade. Our findings suggest an inverse relationship between negative Ptiss,O2 and CBF responses, and provide direct in vivo evidence for a tight coupling between activity in postsynaptic AMPA receptors and cerebellar oxygen consumption.

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