GABAergic Neurons in Barrel Cortex Show Strong, Whisker-Dependent Metabolic Activation during Normal Behavior

Abstract

Electrophysiological data from the rodent whisker/barrel cortex indicate that GABAergic, presumed inhibitory, neurons respond more vigorously to stimulation than glutamatergic, presumed excitatory, cells. However, these data represent very small neuronal samples in restrained, anesthetized, or narcotized animals or in cortical slices. Histochemical data from primate visual cortex, stained for the mitochondrial enzyme cytochrome oxidase (CO) and for GABA, show that GABAergic neurons are more highly reactive for CO than glutamatergic cells, indicating that inhibitory neurons are chronically more active than excitatory neurons but leaving doubt about the short-term stimulus dependence of this activation. Taken together, these results suggest that highly active inhibitory neurons powerfully influence relatively inactive excitatory cells but do not demonstrate directly the relative activities of excitatory and inhibitory neurons in the cortex during normal behavior.We used a novel double-labeling technique to approach the issue of excitatory and inhibitory neuronal activation during behavior. Our technique combines high-resolution 2-deoxyglucose (2DG), immunohistochemical staining for neurotransmitterspecific antibodies, and automated image analysis to collect the data. We find that putative inhibitory neurons in barrel cortex of behaving animals are, on average, much more heavily 2DG-labeled than presumed excitatory cells, a pattern not seen in animals anesthetized at the time of 2DG injection. This metabolic activation is dependent specifically on sensory inputs from the whiskers, because acute trimming of most whiskers greatly reduces 2DG labeling in both cell classes in columns corresponding to trimmed whiskers. Our results provide confirmation of the active GABAergic cell hypothesis suggested by CO and single-unit data. We conclude that strong activation of inhibitory cortical neurons must confer selective advantages that compensate for its inherent energy inefficiency.

Diverse Types of Interneurons Generate Thalamus-Evoked Feedforward Inhibition in the Mouse Barrel Cortex

“…This finding is in agreement with previous data in vivo showing that, compared with excitatory neurons, putative inhibitory neurons respond more vigorously, at lower thresholds, and with shorter latencies (Simons, 1978;Yamamoto et al, 1988;Simons and Carvell, 1989;Swadlow, 1989;Welker et al, 1993) and are metabolically more active (Nie and Wong-Riley, 1995;McCasland and Hibbard, 1997). It was previously suggested (Simons, 1995) that the thalamocortical synapses may be more effective on inhibitory neurons because they impinge on their Figure 6.…”

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

“…18,76 Few studies from hippocampus and neocortex provide first evidence that (i) glucose metabolism is increased during long-term recurrent inhibition of hippocampal pyramidal cells, 81 (ii) the contribution of GABA to the glutamate/GABA-glutamine cycle might account for 10% to 15% of the total oxidative metabolism 82 and (iii) glucose metabolism might be significantly stronger in GABAergic neurons than in glutamatergic neurons as revealed by combining high-resolution 2-deoxyglucose and immunohistochemistry. 83 For the latter technically advanced study with single-cell resolution, the methodological obstacles such as adequate label retention during immunohistochemical processing that may limit interpretation have been discussed. 83,84 For the remainder of this review, we will summarize current knowledge on the role of interneurons in cortical high-frequency oscillations, in particular, gamma oscillations, and on the possible neuroenergetical and pathophysiological implications of high energy utilization in a specific subset of these GABAergic cells, i.e., fast-spiking, parvalbumin-positive (PV þ ) interneurons.…”

“…83 For the latter technically advanced study with single-cell resolution, the methodological obstacles such as adequate label retention during immunohistochemical processing that may limit interpretation have been discussed. 83,84 For the remainder of this review, we will summarize current knowledge on the role of interneurons in cortical high-frequency oscillations, in particular, gamma oscillations, and on the possible neuroenergetical and pathophysiological implications of high energy utilization in a specific subset of these GABAergic cells, i.e., fast-spiking, parvalbumin-positive (PV þ ) interneurons.…”

A Paradigm Shift in Functional Brain Imaging

“…Complementary analyses using extant anatomic, physiologic, and metabolic data (Wong-Riley, 1989;Ames, 2000;Attwell and Laughlin, 2001;Lennie, 2003) to assess the cost of different components of excitatory signaling in the gray matter have arrived at similar conclusions. Such estimates leave for future consideration the demands placed on the brain's energy budget by the functional activity of inhibitory interneurons (Ackermann et al, 1984;McCasland and Hibbard, 1997;Waldvogel et al, 2000;Chatton et al, 2003;Patel et al, 2005;Buzsáki et al, 2007) and astrocytes (Pellerin and Magistretti, 1997;Magistretti and Chatton, 2005). That evidence notwithstanding, it is likely to remain the case that the majority of brain energy consumption is devoted to functionally significant intrinsic activity.…”