Inhibitory interneurons in a cortical column form hot zones of inhibition in layers 2 and 5A

Abstract

Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in cortical columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The "hot zones" of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.F or a quantitative understanding of the interaction between excitatory and inhibitory synaptic transmission in the neocortex, it is crucial to obtain data on the absolute numbers and the relative distribution of excitatory and inhibitory (mostly GABAergic) neurons [interneurons (INs)] in a cortical column. Only on the basis of such prevalence numbers is it possible to interpret data on single-cell physiology (1-8) and synaptic connections of pairs of neurons (9-12) at the circuit level. The distribution of cortical neurons and INs has therefore been the objective of several studies over the past decades (13-15). Statistical sampling methods were used because mapping tens of thousands of neurons was not feasible. Although the nominal error bounds of such methods are in the range of 10-20%, the reported absolute numbers differed strongly among studies, especially for sparse neuron populations, such as INs and their subtypes. The ratio of INs reported for the somatosensory cortex varied between 15% and 25%, thus by almost a factor of 2 (13,16,17). Data on possible differences in IN density between layers in a cortical column were contradictory (13,15,16,18,19).To resolve these substantial discrepancies, we undertook the complete mapping of INs in entire cortical columns using the cytoarchitectonic barrels in L4 as a reference frame for the thalamocortical innervation volume (20) in postnatal day (P) 25-36 rat vibrissal cortex. Our data show that the overall prevalence of inhibitory neurons was previously overestimated by almost a factor of 2. We find a unique substructure of the distribution of INs in a cortical column that can explain the layer-specific differences in the excitability in neocortex. The distribution of INs defines layer 2 as a distinct neocortical layer.

Mirror neurons in monkey area F5 do not adapt to the observation of repeated actions

“…However, why should the balance of excitatory/ inhibitory inputs differ between mirror neurons and neurons in visual cortex? Our again speculative answer is that this may be a consequence of subtle architectural differences between visual and premotor cortex 50 .…”

Scaling of Topologically Similar Functional Modules Defines Mouse Primary Auditory and Somatosensory Microcircuitry

“…greater accuracy as they are maximized with increased sample size (Milo et al, 2002). Because temporal resolution of multiphoton microscopy is compromised at these spatial scales, we used the heuristically optimized path scan technique (Sadovsky et al, 2011;Fig.…”

“…We examined the spatial extent of each functional circuit by reprojecting circuit events into anatomical space. We identified lamina, and anatomical columns in S1BF (Lefort et al, 2009;Meyer et al, 2011), in 69% of our imaged field of views (see Materials and Methods; Fig. 4A).…”

“…We chose a comparative methodology (Kätzel et al, 2010;Yang and Zador, 2012) to examine the microcircuit postulate by comparing functional wiring diagrams generated from primary auditory (A1) and somatosensory barrel field (S1BF) neocortex. These two regions are an interesting test of the microcircuit hypothesis as both map sensory input anatomically and display temporally structured circuit activity (Luczak et al, 2007;Montemurro et al, 2007), but each area appears organized according to different design principles. A1 can be considered a one-dimensional tonotopic mapping of the cochlea along the rostrocaudal axis (Bandyopadhyay et al, 2010; Oviedo et al, 2010;Rothschild et al, 2010;Levy and Reyes, 2012), whereas S1BF provides a twodimensional mapping along both the rostrocaudal and dorsoventral axes corresponding to the spatial location of the whiskers, manifested in a clear columnar organization containing barrels (Woolsey and Van der Loos, 1970;Welker, 1976;Simons, 1997;Lefort et al, 2009).…”

“…It is clear that microcircuitry in the neocortex is structured (Song et al, 2005;Yoshimura et al, 2005;Perin et al, 2011;Levy and Reyes, 2012); however, it is unknown how this structure manifests functionally particularly at the larger mesoscale throughout the neocortex. Elucidating the organization of functional circuitry (Gerstein et al, 1978) will provide key insights into the flow of activity through local neocortical circuitry, the underlying circuit architecture, and also has the potential to provide insight into the computational strategies used in each respective cortical region (Watts and Strogatz, 1998;Alon, 2007).…”