Pathway-Specific Variations in Neurovascular and Neurometabolic Coupling in Rat Primary Somatosensory Cortex

Enager, Pia; Piilgaard, Henning; Offenhauser, Nikolas; Kocharyan, Ara; Fernandes, Priscilla; Hamel, Edith; Lauritzen, Martin

doi:10.1038/jcbfm.2009.23

Cited by 94 publications

(78 citation statements)

References 45 publications

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“…Another contributing factor could be that PV neurons receive depressing glutamatergic input from the thalamus (Tan et al, 2008). Hence, our findings, together with recent studies on different subcortical or corticocortical afferent pathways and ensuing hypermic responses (Kocharyan et al, 2008;Enager et al, 2009), emphasize that the activated cortical circuitry is both afferent and stimulus specific, as distinct subsets of cortical neurons were recruited depending on the input.…”

Section: Identity Of the Cortical Neuronal Circuitry Recruited By Whimentioning

confidence: 64%

“…Therefore, understanding the cellular basis of the activated neurocircuitry is essential for adequate interpretation of brain imaging data. A growing body of evidence suggests that both excitatory and inhibitory neurons govern the hemodynamic response to increased neuronal activity (Niessing et al, 2005;Kocharyan et al, 2008;Enager et al, 2009). However, the identity of the neurons recruited by a given afferent input, their interaction with astrocytes, and the mechanisms by which their activation results in changes in CBF remain largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

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Pyramidal Neurons Are "Neurogenic Hubs" in the Neurovascular Coupling Response to Whisker Stimulation

Lecrux

Toussay

Kocharyan

et al. 2011

Journal of Neuroscience

157

165

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The whisker-to-barrel cortex is widely used to study neurovascular coupling, but the cellular basis that underlies the perfusion changes is still largely unknown. Here, we identified neurons recruited by whisker stimulation in the rat somatosensory cortex using double immunohistochemistry for c-Fos and markers of glutamatergic and GABAergic neurons, and investigated in vivo their contribution along with that of astrocytes in the evoked perfusion response. Whisker stimulation elicited cerebral blood flow (CBF) increases concomitantly with c-Fos upregulation in pyramidal cells that coexpressed cyclooxygenase-2 (COX-2) and GABA interneurons that coexpressed vasoactive intestinal polypeptide and/or choline acetyltransferase, but not somatostatin or parvalbumin. The evoked CBF response was decreased by blockade of NMDA (MK-801, Ϫ37%), group I metabotropic glutamate (MPEPϩLY367385, Ϫ40%), and GABA-A (picrotoxin, Ϫ31%) receptors, but not by GABA-B, VIP, or muscarinic receptor antagonism. Picrotoxin decreased stimulus-induced somatosensory evoked potentials and CBF responses. Combined blockade of GABA-A and NMDA receptors yielded an additive decreasing effect (Ϫ61%) of the evoked CBF compared with each antagonist alone, demonstrating cooperation of both excitatory and inhibitory systems in the hyperemic response. Blockade of prostanoid synthesis by inhibiting COX-2 (indomethacin, NS-398), expressed by ϳ40% of pyramidal cells but not by astrocytes, impaired the CBF response (Ϫ50%). The hyperemic response was also reduced (Ϫ40%) after inhibition of astroglial oxidative metabolism or epoxyeicosatrienoic acids synthesis. These results demonstrate that changes in pyramidal cell activity, sculpted by specific types of inhibitory GABA interneurons, drive the CBF response to whisker stimulation and, further, that metabolically active astrocytes are also required.

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Section: Identity Of the Cortical Neuronal Circuitry Recruited By Whimentioning

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Pyramidal Neurons Are "Neurogenic Hubs" in the Neurovascular Coupling Response to Whisker Stimulation

Lecrux

Toussay

Kocharyan

et al. 2011

Journal of Neuroscience

157

165

View full text Add to dashboard Cite

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“…Interestingly, several studies indicate that GABAergic interneurons, including PV þ interneurons participate in regulating hemodynamic responses. [129][130][131] Moreover, the oxygen overshoot during the activity-dependent hemodynamic response might serve the upkeep of sufficient oxygen levels in mitochondria of fast-spiking interneurons, particularly when located in some distance from the vasculature. 132,133 Why would fast-spiking interneurons need higher amounts of energy than more scarcely spiking principal cells or other types of interneurons?…”

Section: Interneuron Energy Hypothesis O Kann Et Almentioning

confidence: 99%

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

Kann

Papageorgiou

Draguhn

2014

J Cereb Blood Flow Metab

236

235

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Gamma oscillations (B30 to 100 Hz) provide a fundamental mechanism of information processing during sensory perception, motor behavior, and memory formation by coordination of neuronal activity in networks of the hippocampus and neocortex. We review the cellular mechanisms of gamma oscillations about the underlying neuroenergetics, i.e., high oxygen consumption rate and exquisite sensitivity to metabolic stress during hypoxia or poisoning of mitochondrial oxidative phosphorylation. Gamma oscillations emerge from the precise synaptic interactions of excitatory pyramidal cells and inhibitory GABAergic interneurons. In particular, specialized interneurons such as parvalbumin-positive basket cells generate action potentials at high frequency ('fast-spiking') and synchronize the activity of numerous pyramidal cells by rhythmic inhibition ('clockwork'). As prerequisites, fast-spiking interneurons have unique electrophysiological properties and particularly high energy utilization, which is reflected in the ultrastructure by enrichment with mitochondria and cytochrome c oxidase, most likely needed for extensive membrane ion transport and g-aminobutyric acid metabolism. This supports the hypothesis that highly energized fast-spiking interneurons are a central element for cortical information processing and may be critical for cognitive decline when energy supply becomes limited ('interneuron energy hypothesis'). As a clinical perspective, we discuss the functional consequences of metabolic and oxidative stress in fast-spiking interneurons in aging, ischemia, Alzheimer's disease, and schizophrenia.

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“…α=.29 [22] and β=1.5 [20] were used. We used CMRO 20 =256.9±11.5 μmol/100 g/ min [23] and CBF 0 =0.4, 0.69 and 0.91 ml/g per minute (Table 1). M reflects the baseline deoxyHb content and is also defined as the maximum BOLD change for the baseline state in the region of interest.…”

Section: Modeling Bold Responses From Cbf and Cmro 2 Data In The Barrmentioning

confidence: 99%

“…CBF and CMRO 2 changes as a function of stimulus frequency measured in the rat barrel cortex following trigeminal nerve stimulation as described in [23] were used to model BOLD responses.…”

Section: Modeling Bold Responses From Cbf and Cmro 2 Data In The Barrmentioning

confidence: 99%

BOLD responses to trigeminal nerve stimulation

Just

Petersen

Gruetter

2010

Magnetic Resonance Imaging

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The current study investigates a new model of barrel cortex activation using stimulation of the infraorbital branch of the trigeminal nerve. A robust and reproducible activation of the rat barrel cortex was obtained following trigeminal nerve stimulation. Blood oxygen leveldependent (BOLD) effects were obtained in the primary somatosensory barrel cortex (S1BF), the secondary somatosensory cortex (S2) and the motor cortex. These cortical areas were reached from afferent pathways from the trigeminal ganglion, the trigeminal nuclei and thalamic nuclei from which neurons project their axons upon whisker stimulation. The maximum BOLD responses were obtained for a stimulus frequency of 1 Hz, a stimulus pulse width of 100 μs and for current intensities between 1.5 and 3 mA. The BOLD response was nonlinear as a function of frequency and current intensity. Additionally, modeling BOLD responses in the rat barrel cortex from separate cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO 2 ) measurements showed good agreement with the shape and amplitude of measured BOLD responses as a function of stimulus frequency and will potentially allow to identify the sources of BOLD nonlinearities. Activation of the rat barrel cortex using trigeminal nerve stimulation will contribute to the interpretation of the BOLD signals from functional magnetic resonance imaging studies.

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Pathway-Specific Variations in Neurovascular and Neurometabolic Coupling in Rat Primary Somatosensory Cortex

Cited by 94 publications

References 45 publications

Pyramidal Neurons Are "Neurogenic Hubs" in the Neurovascular Coupling Response to Whisker Stimulation

Pyramidal Neurons Are "Neurogenic Hubs" in the Neurovascular Coupling Response to Whisker Stimulation

Highly Energized Inhibitory Interneurons are a Central Element for Information Processing in Cortical Networks

BOLD responses to trigeminal nerve stimulation

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