Long-Range GABAergic Connections Distributed throughout the Neocortex and their Possible Function

Abstract

Features and functions of long-range GABAergic projection neurons in the developing cerebral cortex have been reported previously, although until now their significance in the adult cerebral cortex has remained uncertain. The septo-hippocampal circuit is one exception – in this system, long-range mature GABAergic projection neurons have been well analyzed and their contribution to the generation of theta-oscillatory behavior in the hippocampus has been documented. To have a clue to the function of the GABAergic projection neurons in the neocortex, we view how the long-range GABAergic projections are integrated in the cortico-cortical, cortico-fugal, and afferent projections in the cerebral cortex. Then, we consider the possibility that the GABAergic projection neurons are involved in the generation, modification, and/or synchronization of oscillations in mature neocortical neuron activity. When markers that identify the GABAergic projection neurons are examined in anatomical and developmental studies, it is clear that neuronal NO synthetase (nNOS)-immunoreactivity can readily identify GABAergic projection neurons. GABAergic projection neurons account for 0.5% of the neocortical GABAergic neurons. To elucidate the role of the GABAergic projection neurons in the neocortex, it will be necessary to clarify the network constructed by nNOS-positive GABAergic projection neurons and their postsynaptic targets. Thus, our long-range goals will be to label and manipulate (including deleting) the GABAergic projection neurons using genetic tools driven by a nNOS promoter. We recognize that this may be a complex endeavor, as most excitatory neurons in the murine neocortex express nNOS transiently. Nevertheless, additional studies characterizing long-range GABAergic projection neurons will have great value to the overall understanding of mature cortical function.

5-HT3AReceptor-Bearing White Matter Interstitial GABAergic Interneurons Are Functionally Integrated into Cortical and Subcortical Networks

“…Previous studies reported the presence of longrange GABAergic projection neurons in the white matter. Most of these cells express nNOS, NPY, and somatostatin (Tomioka et al, 2005;Higo et al, 2007Higo et al, , 2009Tomioka and Rockland, 2007;Tamamaki and Tomioka, 2010) and are not identical with the cell population characterized in this study. Interestingly, some EGFP-positive WMICs have dendrites in the striatum and hippocampus and axons reaching into the cortex.…”

Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights

“…Subplate neurons are probable candidates for hub neurons in the developing cortex given that this transient cortical region was recently identified as a 'hub station' [103]. In addition, hippocampal hub cells share several remarkable properties with subsets of subplate neurons, including long distance projections and the ability to drive synchronization in the developing cortical plate [103][104][105].…”

Spontaneous cortical activity alternates between motifs defined by regional axonal projections

“…We used positive correlation to examine areas that are co-activated. It may also be possible to examine areas that are negatively correlated where one region may inhibit another 45 .…”

“…However, most inhibitory projections do not span long distances 45 . More detailed analysis of cortical activity 46 will likely reveal cortical layer specific functional connections that may be influenced by local intracortical inhibition.…”