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Pasted below is something I recently wrote on the physiology underlying functional imaging activations in the cerebellum. I suggest you read it only if you are particularly interested in imaging the cerebellum! Best wishes Sarah Geraint's findings hold for visual cortex, and might generalise to other parts of the cortex. However,to what increases in blood flow or BOLD signal in the cerebellum correspond, in terms of neuronal activity, is less well understood. One possibility is that the principal cells of the cerebellar cortex, the Purkinje cells, which are inhibitory, account for changes in blood flow in the cerebellum. However, recently it has been found that, in rats, there is no simple correlation between blood flow and Purkinje cell firing (Mathiesen et al, 1998). Mathiesen and colleagues had two important findings. Firstly, they found that there is a blood flow increase evoked by stimulating the parallel fibres (i.e. the granule cell axons), which is inhibited by AMPA receptor blockers. Since glutamate acts on the AMPA receptors, this suggests that it is glutamate release from the granule cell terminals, which acts on AMPA receptors to evoke a blood flow increase. In the cerebellar cortex there are AMPA receptors on Purkinje cells, inhibitory cells, and on Bergmann glia, and in principle it could be any of these, or the downstream consequences of their activation, that trigger the blood flow increase. Secondly, however, the authors showed that parallel fibre stimulation decreases Purkinje cell spiking. This is because stimulating the parallel fibres activates inhibitory interneurons, which send inhibitory synapses to Purkinje cells. This inhibitory innervation outweighs the effect of the direct excitatory input from the parallel fibres. Indeed, blocking GABA receptors (which mediate the inhibition) blocks the effect on Purkinje cell firing but not the increase of blood flow. Therefore, it is not Purkinje cell firing that leads to the blood flow increase. The authors suggest that it is the inhibitory inter-neuronal firing that causes an increase in blood flow. However, the cerebellum is a multi-layered structure containing various types of cell and there are also several other possibilities that could cause an increase blood flow. A likely downstream messenger that could be produced after glutamate activates the AMPA receptors is nitric oxide. There is evidence that in the cerebellum nitric oxide dilates blood vessels by generating cGMP in the cells controlling vessel diameter. Thus, glutamate that is released from parallel fibres and acts on Purkinje cells can raise calcium locally in Purkinje cell dendrites. This brings about a release of nitric oxide, which dilates blood vessels, independently of the change in Purkinje cell firing that occurs. In summary, blood flow increases could be triggered either by inhibitory inter-neuronal firing or by glutamate, which is released from the parallel fibres and acts on AMPA receptors, or by both of these factors. Which of these factors controls blood flow in the cerebellum is unknown and this question is further complicated by the interaction with activity in other cerebellar cells. For example, an increase of granule cell firing might lead to an increase or decrease of Purkinje cell firing. Therefore if blood flow correlates with granule cell firing, it might also correlate with Purkinje cell firing. In addition it is possible that granule cell firing might also correlate with mossy fibre input firing if an increase of mossy fibre input always leads to an increase of granule cell firing. This is complicated because the mossy fibres both excite the granule cells directly and inhibit them through Golgi cells. Thus, it is unlikely that BOLD signal, or blood flow, in the cerebellum corresponds simply to an increase in firing of the Purkinje cells. Mathiesen, C., Caesar, K., Akgoren, N. & Lauritzen, M. (1998). Modification of activity-dependent increases of cerebral blood flow by excitatory synaptic activity and spikes in rat cerebellar cortex. Journal of Physiology (London) 512 (Pt 2), 555-66. >Dear List >When someone undergos a particular cognitive activation task (eg a verbal >fluency test for sake of argument) and SPM finds 'activations' and >'deactivations' relative to a control condition, what are the principle >contributors at the cellular and synaptic level to this increase or >decrease in >metabolic requirements in the region identified? > >For example, is it mainly the metabolic requirements related to >glutamate/other EAAs release and reuptake or are other identified >neurotransmitters equally or more important etc etc. Are the relevant >contributions of neuronal vs glial metablism known? > >And am I even right to assume that the 'activation' represents mainly synaptic >activity as opposed to, say, cell body metabolism? > >While the question is not completely SPM-related, I'd be grateful for any info >or to be pointed towards relevant references. > >Thanks in advance. > >Peter Talbot -- DR S-J BLAKEMORE Mental Processes and Brain Activation INSERM Unit 280 151 Cours Albert-Thomas 69424 Lyon Cedex 3 France Tél: 00 33 (0)4 72 68 19 05 Fax: 00 33 (0)4 72 68 19 02 Email: [log in to unmask] http://www.fil.ion.ucl.ac.uk/groups/Frith/Sarah.html