Modification of activity‐dependent increases of cerebral blood flow by excitatory synaptic activity and spikes in rat cerebellar cortex

Abstract

Mechanisms of activity‐dependent increases in cerebral blood flow (CBF) were examined in rat cerebellar cortex using the laser Doppler flow technique and extracellular recordings of single unit activity and field potentials. Stimulation of the monosynaptic climbing fibre system evoked long‐lasting complex spikes in Purkinje cells, and extracellular field potentials with a characteristic profile that indicated contributions from both passive and active membrane mechanisms. The concomitant CBF increases were reproducible at fairly short intervals, and suggest that both synaptic activity and spikes may contribute to increased CBF. Stimulation of the disynaptic parallel fibre system inhibited the spiking activity in Purkinje cells, while the postsynaptic activity increased as indicated by the simultaneously recorded field potential. Nevertheless, CBF always increased. The inhibition of spike firing activity was partly dependent on GABAergic transmission, but may also relate to the intrinsic membrane properties of Purkinje cells. The CBF increases evoked by parallel or climbing fibre stimulation were highly correlated to the sum of neural activities, i.e. the negativity of field potentials multiplied by the stimulus frequency. This suggests a robust link between extracellular current flow and activity‐dependent increases in CBF. AMPA receptor blockade attenuated CBF increases and field potential amplitudes, while NMDA receptor antagonism did not. This is consistent with the idea that the CBF responses are of neuronal origin. This study has shown that activity‐dependent CBF increases evoked by stimulation of cerebellar parallel fibres are dependent on synaptic excitation, including excitation of inhibitory interneurones, whereas the net activity of Purkinje cells, the principal neurones of the cerebellar cortex, is unimportant for the vascular response. For the climbing fibre system, not only synaptic activity but also the generation of complex spikes from Purkinje cells contribute to the increases in CBF. The strong correlation between CBF and field potential amplitudes suggests that extracellular ion fluxes contribute to the coupling of brain activity to blood flow.

Changes in reward-related signals in the rat nucleus accumbens measured by in vivo oxygen amperometry are consistent with fMRI BOLD responses in man

“…The relationship between neuronal activity and haemodynamic response is still a question under considerable debate (Attwell and Iadecola, 2002;Lauritzen, 2005;Logothetis et al, 2001). However, several studies have shown that increases in local CBF are mainly driven by afferent input to regions of interest (Logothetis et al, 2001;Mathiesen et al, 1998) and are therefore best correlated to local field potentials rather than spiking activity (Masamoto et al, 2008;Mathiesen et al, 1998). It is then plausible that the amperometric signal could be driven by a haemodynamic response subsequent to dopaminergic terminal release and changes in local field activity in the NAc induced by midbrain dopamine neurons.…”

Coupling between somatosensory evoked potentials and hemodynamic response in the rat

“…This is probably because the majority of the synapses within a column input from other neurons in the cortex, and the hemodynamic response is mostly sensitive to the level of synaptic activity (Mathiesen et al, 1998).…”

“…Recently, a great deal of effort has been devoted to studying the nature of the neurovascular coupling by combining invasive electrophysiological measurements of multiunit activity (MUA) and local field potentials (LFP) with measurements of hemoglobin concentration changes using intrinsic optical imaging and spectroscopy (OIS) (Devor et al, 2003;Sheth et al, 2003) or with measurements of cerebral blood flow (CBF) changes using laser Doppler flowmetry (LDF) (Hoffmeyer et al, 2007;Jones et al, 2001;Mathiesen et al, 1998;Ngai et al, 1999;Thomsen et al, 2004;Ureshi et al, 2004). Despite technical difficulties, progress has been made in combining microelectrode recordings of MUA and LFP, or evoked potentials measured on the scalp, with BOLD fMRI (Logothetis et al, 2001).…”

How accurate is magnetic resonance imaging of brain function?

“…The current status of these issues has been reviewed recently [62]. In regard to spatial specificity, most notable are the concepts that fMRI imaging signals might be linked more to a large population of neurons displaying alterations in their postsynaptic potentials (as reflected in local field potentials) than to phasic spiking output [63][64][65][66].…”