Ongoing Neuronal Activity Research Articles

K+ depolarization evokes ATP, adenosine and glutamate release from glia in rat hippocampus: a microelectrode biosensor study

This study was undertaken to characterize the ATP, adenosine and glutamate outflow evoked by depolarization with high K(+) concentrations, in slices of rat hippocampus. We utilized the microelectrode biosensor technique and extracellular electrophysiological recording for the real-time monitoring of the efflux of ATP, adenosine and glutamate. ATP, adenosine and glutamate sensors exhibited transient and reversible current during depolarization with 25 mM K(+) , with distinct kinetics. The ecto-ATPase inhibitor ARL67156 enhanced the extracellular level of ATP and inhibited the prolonged adenosine efflux, suggesting that generation of adenosine may derive from the extracellular breakdown of ATP. Stimulation-evoked ATP, adenosine and glutamate efflux was inhibited by tetrodotoxin, while exposure to Ca(2+) -free medium abolished ATP and adenosine efflux from hippocampal slices. Extracellular elevation of ATP and adenosine were decreased in the presence of NMDA receptor antagonists, D-AP-5 and ifenprodil, whereas non-NMDA receptor blockade by CNQX inhibited glutamate but not ATP and adenosine efflux. The gliotoxin fluoroacetate and P2X7 receptor antagonists inhibited the K(+) -evoked ATP, adenosine and glutamate efflux, while carbenoxolone in low concentration and probenecid decreased only the adenosine efflux. Our results demonstrated activity-dependent gliotransmitter release in the hippocampus in response to ongoing neuronal activity. ATP and glutamate were released by P2X7 receptor activation into extracellular space. Although the increased extracellular levels of adenosine did derive from released ATP, adenosine might also be released directly via pannexin hemichannels.

Highlights from the Literature

Highlights from the Literature

The inflammatory reflex: the current model should be revised

The inflammatory reflex: the current model should be revised

Agonist of 5-HT1A/7 receptors but not that of 5-HT2 receptors disinhibits tracheobronchial-projecting airway vagal preganglionic neurons of rats

The vagus nerves supply the major cholinergic tone to airway smooth muscles physiologically and play critical roles in the genesis of airway hyperreactivity under some pathological conditions. Postganglionic airway cholinergic tone relies largely on the ongoing activity of medullary airway vagal preganglionic neurons (AVPNs), of which the tracheobronchial-projecting ones are primarily located in the external formation of the nucleus ambiguus (eNA). AVPNs are regulated by 5-HT, and 5-HT1A/7 and 5-HT2 receptors have been indicated to be involved. But the mechanisms at synaptic level are unknown. In the present study, tracheobronchial-projecting AVPNs (T-AVPNs) were retrogradely labeled from the trachea wall; fluorescently labeled T-AVPNs in the eNA were recorded with whole-cell voltage patch clamp; and the effects of 5-HT1A/7 receptor agonist (±)-8-Hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT) (1 μmol L−1) and 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10 μmol L−1) on the synaptic inputs were examined. 8-OH-DPAT significantly inhibited the GABAergic and glycinergic spontaneous inhibitory postsynaptic currents (sIPSCs) of T-AVPNs in both the frequency and amplitude but had no effect on the GABAergic and glycinergic miniature inhibitory postsynaptic currents (mIPSCs). The 8-OH-DPAT inhibition of the GABAergic and glycinergic sIPSCs was prevented by 5-HT1A/7 receptor antagonist N-[2-[4-(2-Methoxyphenyl)-1-piperazinyl] ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY-100635) (1 μmol L−1). 8-OH-DPAT had no effect on the glutamatergic spontaneous excitatory postsynaptic currents (sEPSCs) and caused no alterations in the baseline current and input resistance of T-AVPNs. DOI had no effect on any types of the synaptic inputs of T-AVPNs. These results suggest that 5-HT1A/7 receptor agonist causes “disinhibition” of T-AVPNs, which might, in part, account for the reflex increase of airway resistance.

Peripheral and Central Inputs Shape Network Dynamics in the Developing Visual Cortex In Vivo

Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.

Hemodynamic Responses Evoked by Neuronal Stimulation via Channelrhodopsin-2 Can Be Independent of Intracortical Glutamatergic Synaptic Transmission

Maintenance of neuronal function depends on the delivery of oxygen and glucose through changes in blood flow that are linked to the level of ongoing neuronal and glial activity, yet the underlying mechanisms remain unclear. Using transgenic mice expressing the light-activated cation channel channelrhodopsin-2 in deep layer pyramidal neurons, we report that changes in intrinsic optical signals and blood flow can be evoked by activation of a subset of channelrhodopsin-2-expressing neurons in the sensorimotor cortex. We have combined imaging and pharmacology to examine the importance of glutamatergic synaptic transmission in this form of neurovascular coupling. Blockade of ionotropic glutamate receptors with the antagonists CNQX and MK801 significantly reduced forepaw-evoked hemodynamic responses, yet resulted in no significant reduction of channelrhodopsin-evoked hemodynamic responses, suggesting that stimulus-dependent coupling of neuronal activity to blood flow can be independent of local excitatory synaptic transmission. Together, these results indicate that channelrhodopsin-2 activation of sensorimotor excitatory neurons produces changes in intrinsic optical signals and blood flow that can occur under conditions where synaptic activation of neurons or other cells through ionotropic glutamate receptors would be blocked.

Spinal trigeminal neurons demonstrate an increase in responses to dural electrical stimulation in the orofacial formalin test

Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term “orofacial pain” (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache—the orofacial formalin test and the model of trigeminovascular nociception—to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache.

The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus

Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5min) and sacrificed 15min after the end of stress. Real-time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience

Multi-electrode Array Recordings of Neuronal Avalanches in Organotypic Cultures

The cortex is spontaneously active, even in the absence of any particular input or motor output. During development, this activity is important for the migration and differentiation of cortex cell types and the formation of neuronal connections1. In the mature animal, ongoing activity reflects the past and the present state of an animal into which sensory stimuli are seamlessly integrated to compute future actions. Thus, a clear understanding of the organization of ongoing i.e. spontaneous activity is a prerequisite to understand cortex function. Numerous recording techniques revealed that ongoing activity in cortex is comprised of many neurons whose individual activities transiently sum to larger events that can be detected in the local field potential (LFP) with extracellular microelectrodes, or in the electroencephalogram (EEG), the magnetoencephalogram (MEG), and the BOLD signal from functional magnetic resonance imaging (fMRI). The LFP is currently the method of choice when studying neuronal population activity with high temporal and spatial resolution at the mesoscopic scale (several thousands of neurons). At the extracellular microelectrode, locally synchronized activities of spatially neighbored neurons result in rapid deflections in the LFP up to several hundreds of microvolts. When using an array of microelectrodes, the organizations of such deflections can be conveniently monitored in space and time. Neuronal avalanches describe the scale-invariant spatiotemporal organization of ongoing neuronal activity in the brain2,3. They are specific to the superficial layers of cortex as established in vitro4,5, in vivo in the anesthetized rat 6, and in the awake monkey7. Importantly, both theoretical and empirical studies2,8-10 suggest that neuronal avalanches indicate an exquisitely balanced critical state dynamics of cortex that optimizes information transfer and information processing.In order to study the mechanisms of neuronal avalanche development, maintenance, and regulation, in vitro preparations are highly beneficial, as they allow for stable recordings of avalanche activity under precisely controlled conditions. The current protocol describes how to study neuronal avalanches in vitro by taking advantage of superficial layer development in organotypic cortex cultures, i.e. slice cultures, grown on planar, integrated microelectrode arrays (MEA; see also 11-14).

Multi-electrode Array Recordings of Neuronal Avalanches in Organotypic Cultures

The cortex is spontaneously active, even in the absence of any particular input or motor output. During development, this activity is important for the migration and differentiation of cortex cell types and the formation of neuronal connections1. In the mature animal, ongoing activity reflects the past and the present state of an animal into which sensory stimuli are seamlessly integrated to compute future actions. Thus, a clear understanding of the organization of ongoing i.e. spontaneous activity is a prerequisite to understand cortex function. Numerous recording techniques revealed that ongoing activity in cortex is comprised of many neurons whose individual activities transiently sum to larger events that can be detected in the local field potential (LFP) with extracellular microelectrodes, or in the electroencephalogram (EEG), the magnetoencephalogram (MEG), and the BOLD signal from functional magnetic resonance imaging (fMRI). The LFP is currently the method of choice when studying neuronal population activity with high temporal and spatial resolution at the mesoscopic scale (several thousands of neurons). At the extracellular microelectrode, locally synchronized activities of spatially neighbored neurons result in rapid deflections in the LFP up to several hundreds of microvolts. When using an array of microelectrodes, the organizations of such deflections can be conveniently monitored in space and time. Neuronal avalanches describe the scale-invariant spatiotemporal organization of ongoing neuronal activity in the brain2,3. They are specific to the superficial layers of cortex as established in vitro4,5, in vivo in the anesthetized rat 6, and in the awake monkey7. Importantly, both theoretical and empirical studies2,8-10 suggest that neuronal avalanches indicate an exquisitely balanced critical state dynamics of cortex that optimizes information transfer and information processing. In order to study the mechanisms of neuronal avalanche development, maintenance, and regulation, in vitro preparations are highly beneficial, as they allow for stable recordings of avalanche activity under precisely controlled conditions. The current protocol describes how to study neuronal avalanches in vitro by taking advantage of superficial layer development in organotypic cortex cultures, i.e. slice cultures, grown on planar, integrated microelectrode arrays (MEA; see also 11-14).

Differential regulation of Abeta-40 and Abeta-42 extracellular levels by pattern of ongoing neuronal activity

Differential regulation of Abeta-40 and Abeta-42 extracellular levels by pattern of ongoing neuronal activity

On the role of the baseline firing rate in determining the responsiveness of cingulate cortical neurons to iontophoretically applied substance P and acetylcholine.

The relationship between baseline firing rate and the magnitude of excitatory responses to iontophoretically applied substance P (SP) and acetylcholine (ACh) was determined for neurons in the anterior cingulate cortex of the rat. Whereas the size of responses to ACh was positively correlated with the level of ongoing neuronal activity, no correlation, either positive or negative, could be demonstrated for responses to SP. It seems unlikely that the excitatory effects of SP in this brain area result from release of endogenous ACh.

Corrigendum

CorrigendumCorrigendumPublished Online:01 Mar 2011https://doi.org/10.1152/jn.z9k-0648-corr.2011Original articleMoreSectionsPDF (623 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat Volume 104, December 2010 Telenczuk et al. Role of neuronal synchrony in the generation of evoked EEG/MEG responses. J Neurophysiol 104: , 2010; doi:10.1152/jn.00138.2010; http://jn.physiology.org/content/104/6/3557.full.We now substitute the original incorrect Fig. 2 with the corrected figure and accompanying legend. The results and conclusions of this study stand.Fig. 2.Schematic illustration of ongoing neuronal activity and evoked responses generated by means of recruitment of additional oscillators (top, I), microscopic phase reset in an asynchronous population (middle, II), and in a synchronous population (bottom, III). Neuronal recruitment. Ia: schematic representation of a small subpopulation of continuously oscillating neuronal sources (ongoing sources, red cells) and sources that are silent before the onset of the stimulus (transient sources, blue cells). The phases of ongoing sources are random (filling color reflects the instantaneous phase of the oscillation) corresponding to an uniform distribution on a unit circle (polar plot: the angle of each vector encodes the phase of oscillation in a single source, the colored background depicts the mapping of phases to the cells' color shading). Ib: oscillations produced by ongoing (red lines) and transient (blue lines) sources before stimulation. Before the stimulation, no significant ensemble macroscopic activity is observed (thick black line, single trial, not in scale with microscopic activity). Ic: an external stimulus (dashed line denotes stimulus onset) activates the transient sources that produce coherent oscillations that are visible in the ensemble activity (thick black line). Id: schematic representation of the microscopic sources in the poststimulus period (t = 20, for the symbol description, see Ia). The responses to the stimulation are associated with activation of the additional pool of neurons (blue cells) with a narrow distribution of phases (polar plot, blue vectors). Microscopic phase-reset in an asynchronous population. IIa–IId: all labels and symbols in this and following panels are consistent with I. Although prestimulus activity (IIa and IIb) and the macroscopic response (IIc, thick black line) are identical to the neuronal recruitment scenario, the effects of the stimulation are essentially different: here, the transient sources remain silent (IIc, blue lines), but instead the ongoing sources become coherent (IIc, red lines; IId, red vectors in the polar plot), thus summing up constructively to produce visible macroscopic response. Microscopic phase-reset in a synchronized population. IIIa–IIId: the mechanisms of stimulus response are identical to scenario II, but here the ongoing sources are spontaneously synchronized before the stimulation (IIIa). The subsequent stimulation results neither in further increase of the synchrony (compare IIIa with IIId) nor in the consequent change of the amplitude of macroscopic oscillations (compare IIIb with IIIc, thick black line). Nevertheless, the poststimulus macroscopic oscillation is aligned to the stimulus onset independent of its initial phase (note the phase reset at stimulus onset). In all panels, for simplicity, we do not show the slow decay of macroscopic amplitude caused by return of transient sources back to their quiescent state (I) or desynchronization of ongoing sources (II and III).Download figureDownload PowerPointThis article has no references to display. Download PDF Previous Back to Top Next FiguresReferencesRelatedInformationRelated articlesRole of Neuronal Synchrony in the Generation of Evoked EEG/MEG Responses 01 Dec 2010Journal of Neurophysiology More from this issue > Volume 105Issue 3March 2011Pages 1422-1423 Copyright & PermissionsCopyright © 2011 the American Physiological Societyhttps://doi.org/10.1152/jn.z9k-0648-corr.2011History Published online 1 March 2011 Published in print 1 March 2011 Metrics

Non‐psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action

Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB(1) adenosine A(1) and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.

Covert Shift of Attention Modulates the Ongoing Neural Activity in a Reaching Area of the Macaque Dorsomedial Visual Stream

BackgroundAttention is used to enhance neural processing of selected parts of a visual scene. It increases neural responses to stimuli near target locations and is usually coupled to eye movements. Covert attention shifts, however, decouple the attentional focus from gaze, allowing to direct the attention to a peripheral location without moving the eyes. We tested whether covert attention shifts modulate ongoing neuronal activity in cortical area V6A, an area that provides a bridge between visual signals and arm-motor control.Methodology/Principal FindingsWe performed single cell recordings from 3 Macaca Fascicularis trained to fixate straight-head, while shifting attention outward to a peripheral cue and inward again to the fixation point. We found that neurons in V6A are influenced by spatial attention. The attentional modulation occurs without gaze shifts and cannot be explained by visual stimulations. Visual, motor, and attentional responses can occur in combination in single neurons.Conclusions/SignificanceThis modulation in an area primarily involved in visuo-motor transformation for reaching may form a neural basis for coupling attention to the preparation of reaching movements. Our results show that cortical processes of attention are related not only to eye-movements, as many studies have shown, but also to arm movements, a finding that has been suggested by some previous behavioral findings. Therefore, the widely-held view that spatial attention is tightly intertwined with—and perhaps directly derived from—motor preparatory processes should be extended to a broader spectrum of motor processes than just eye movements.

Baseline BOLD correlation predicts individuals' stimulus-evoked BOLD responses

To investigate whether individuals' ongoing neuronal activity at resting state can affect their response to brain stimulation, fMRI BOLD signals were imaged from the human visual cortex of fifteen healthy subjects in the absence and presence of visual stimulation. It was found that the temporal correlation strength but not amplitude of baseline BOLD signal fluctuations acquired under the eyes-fixed condition is positively correlated with the amplitude of stimulus-evoked BOLD responses across subjects. Moreover, the spatiotemporal correlations of baseline BOLD signals imply a coherent network covering the visual system, which is topographically indistinguishable from the “resting-state visual network” observed under the eyes-closed condition. The overall findings suggest that the synchronization of ongoing brain activity plays an important role in determining stimulus-evoked brain activity even at an early stage of the sensory system. The tight relationship between baseline BOLD correlation and stimulus-evoked BOLD amplitude provides an essential basis for understanding and interpreting the large inter-subject BOLD variability commonly observed in numerous fMRI studies and potentially for improving group fMRI analysis. This study highlights the importance to integrate the information from both resting-state coherent networks and task-evoked neural responses for a better understanding of how the brain functions.

A Role for the Ubiquitin–Proteasome System in Activity-Dependent Presynaptic Silencing

Chronic changes in electrical excitability profoundly affect synaptic transmission throughout the lifetime of a neuron. We have previously explored persistent presynaptic silencing, a form of synaptic depression at glutamate synapses produced by ongoing neuronal activity and by strong depolarization. Here we investigate the involvement of the ubiquitin-proteasome system (UPS) in the modulation of presynaptic function. We found that proteasome inhibition prevented the induction of persistent presynaptic silencing. Specifically, application of the proteasome inhibitor MG-132 (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal) prevented decreases in the size of the readily releasable pool of vesicles and in the percentage of active synapses. Presynaptic silencing was accompanied by decreases in levels of the priming proteins Munc13-1 and Rim1. Importantly, overexpression of Rim1alpha prevented the induction of persistent presynaptic silencing. Furthermore, strong depolarization itself increased proteasome enzymatic activity measured in cell lysates. These results suggest that modulation of the UPS by electrical activity contributes to persistent presynaptic silencing by promoting the degradation of key presynaptic proteins.

The Leading Sense: Supramodal Control of Neurophysiological Context by Attention

Attending to a stimulus enhances its neuronal representation, even at the level of primary sensory cortex. Cross-modal modulation can similarly enhance a neuronal representation, and this process can also operate at the primary cortical level. Phase reset of ongoing neuronal oscillatory activity has been shown to be an important element of the underlying modulation of local cortical excitability in both cases. We investigated the influence of attention on oscillatory phase reset in primary auditory and visual cortices of macaques performing an intermodal selective attention task. In addition to responses "driven" by preferred modality stimuli, we noted that both preferred and nonpreferred modality stimuli could "modulate" local cortical excitability by phase reset of ongoing oscillatory activity, and that this effect was linked to their being attended. These findings outline a supramodal mechanism by which attention can control neurophysiological context, thus determining the representation of specific sensory content in primary sensory cortex.

Oscillatory brain states interact with late cognitive components of the somatosensory evoked potential

The question of interaction between ongoing neuronal activity and evoked responses has been addressed for different species, sensory systems and measurement modalities. Among other findings, there is converging evidence for an interaction of occipital alpha-rhythm amplitude with the visual evoked potential. Here, we test the hypothesis that the modulatory role of an ongoing rhythm might not be confined to the visual system and the occipital alpha rhythm, but instead may be generalized to other sensory systems. Using an online EEG analysis approach, we investigated the influence of the Rolandic alpha-rhythm on the somatosensory evoked potential (SEP). We triggered vibrotactile stimulation during periods of high Rolandic alpha-rhythm amplitude. Analysis revealed significant effects of pre-stimulus Rolandic alpha amplitude on the amplitude of the N140 and P260 components of the SEP, known to be linked to cognitive processing, but not on early sensory components. The N140–P260 complex shows a different focus in topography than the early sensory components and the pre-stimulus Rolandic alpha rhythm. These results indicate an involvement of Rolandic alpha-rhythm in higher cognitive processing. In more general terms – and in the context of similar studies in the visual system – our findings suggest that modulation of late EP components by ongoing rhythms might be a characteristic and possibly universal feature of sensory systems.

Principal Cell Spiking, Postsynaptic Excitation, and Oxygen Consumption in the Rat Cerebellar Cortex

One contention within the field of neuroimaging concerns the character of the depicted activity: Does it represent neuronal action potential generation (i.e., spiking) or postsynaptic excitation? This question is related to the metabolic costs of different aspects of neurosignaling. The cerebellar cortex is well suited for addressing this problem because synaptic input to and spiking of the principal cell, the Purkinje cell (PC), are spatially segregated. Also, PCs are pacemakers, able to generate spikes endogenously. We examined the contributions to cerebellar cortical oxygen consumption (CMRO2) of postsynaptic excitation and PC spiking during evoked and ongoing neuronal activity in the rat. By inhibiting excitatory synaptic input using ionotropic glutamate receptor blockers, we found that the increase in CMRO2 evoked by parallel fiber (PF) stimulation depended entirely on postsynaptic excitation. In contrast, PC spiking was largely responsible for the increase in CMRO2 when ongoing neuronal activity was increased by gamma-aminobutyric acid type A receptor blockade. In this case, CMRO2 increased equally during PC spiking with excitatory synaptic activity as during PC pacemaker spiking without excitatory synaptic input. Subsequent inhibition of action potential propagation and neurotransmission by blocking voltage-gated Na+-channels eliminated the increases in CMRO2 due to PF stimulation and increased PC spiking, but left a large fraction of CMRO2, i.e., basal CMRO2, intact. In conclusion, whereas basal CMRO2 in anesthetized animals did not seem to be related to neurosignaling, increases in CMRO2 could be induced by all aspects of neurosignaling. Our findings imply that CMRO2 responses cannot a priori be assigned to specific neuronal activities.