title: Study of neurovascular coupling by modulating neuronal activity with GABA.
abstract: Fundamental to the interpretation of neurovascular coupling is determining the neuronal activity that accounts for functional hyperemia. Recently, synaptic and not spiking activity has been found to be responsible for the hemodynamic response. Using pharmacological manipulation in rats, we want to further determine whether the cortical synaptic activity generated by the thalamic input or the subsequent synaptic activity related to secondary cortical processing is driving the hemodynamic response. In this study, we topically applied γ-aminobutyric acid (GABA) in the somatosensory cortex and used electrical forepaw stimulation to evoke neural and vascular activity. In a group of 8 animals, using laminar electrophysiology, we verified that topical application of GABA for 20min does not affect layer IV synaptic activity but reduces subsequent activity in the supragranular and infragranular layers. In another group of 8 animals, we simultaneously measured the electrical and vascular responses with scalp electroencephalography (EEG) and diffuse optical imaging (DOI), respectively. We decomposed somatosensory evoked potentials (SEP) into three major components: P1, N1, and P2, where P1 represents the thalamic input activity originating in layer IV and N1 and P2 represent the subsequent cortical transmissions. We verified that GABA infusion in the somatosensory cortex does not significantly reduce the P1 SEP component but strongly reduces the N1 and P2 components. We found that GABA also elicits a large reduction in the hemodynamic responses, which correlate with the reduction in N1 and P2 components. These results suggest that the hemodynamic response is predominantly driven by cortico-cortical interactions and not by the initial thalamocortical activity in layer IV.
authors.affiliation: MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital/Harvard Medical School, Charlestown, MA 02129, USA. harsha@nmr.mgh.harvard.edu
authors.forename: Harsha
authors.initials: H
authors.lastname: Radhakrishnan
authors.forename: Weicheng
authors.initials: W
authors.lastname: Wu
authors.forename: David
authors.initials: D
authors.lastname: Boas
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Franceschini
mesh_terms: D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D056324:Diffusion Tensor Imaging / Q000379:methods; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D011237:Predictive Value of Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D013003:Somatosensory Cortex / Q000098:blood supply / Q000166:cytology* / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D005680:gamma-Aminobutyric Acid