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

Ryohei Tomioka,Nobuaki Tamamaki

doi:10.3389/fnins.2010.00202

Ryohei Tomioka, Nobuaki Tamamaki

Open Access

https://doi.org/10.3389/fnins.2010.00202

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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.

Highlights

Neuroanatomical studies in a wide variety of mammals identify two types of cortical neurons, the excitatory glutamatergic neurons, and the inhibitory GABAergic neurons
We would like to explore the possibility that GABAergic interneurons and GABAergic projection neurons are involved in such important brain functions
Retrograde labeling combined with immunohistochemistry of GAD or GABA, or other modified neuronal NO synthetase (nNOS) labeling methods correlated with morphology of retrogradely labeled neurons revealed that GABAergic neurons project axons to remote neocortical regions in the ipsilateral hemisphere (McDonald and Burkhalter, 1993; Albus and Wahle, 1994; Aroniadou-Anderjaska and Keller, 1996; Fabri and Manzoni, 1996) and in the contralateral hemisphere (Peters et al, 1990; Gonchar et al, 1995; Fabri and Manzoni, 2004; Tomioka et al, 2005; Higo et al, 2009)

Summary

Tamamaki and Tomioka

GABAergic projection neuron Neurons which release GABA as an inhibitory transmitter. Usually, GABAergic neurons possess locally ramified axon. In the case of recognizing an event or an object based on perception via multimodal cortical areas, oscillations in multiple cortical areas may need to be synchronized via long-range neuronal connections. These may originate in excitatory neurons, or inhibitory neurons, or both. Gamma-oscillations in multiple cortical areas may be synchronized In this focused review, we would like to explore the possibility that GABAergic interneurons and GABAergic projection neurons are involved in such important brain functions. Medial septal GABAergic neurons are positive for PV and terminate preferentially on hippocampal GABAergic neurons (Freund and Antal, 1988)

NOS CB

FB injection site

Findings

Number of coincident events Number of coincident events