**11. GABAergic cortical interneurons**

Cortical interneurons were first documented with Golgi staining by Santiago Ramón y Cajal and referred to as the "cells with short axons" [60]. Cortical interneurons are typically distin‐ guished by four common attributes: locally projecting, aspiny or sparsely spiny dendrites, small cell soma, and GABAergic. Interneurons exhibit a large diversity and are categorized based on several features including morphology, connectivity, neurochemistry, and physiology [60–62] (**Figure 4**). Due to the heterogeneity of this neuronal population, interneurons can fall into more than one category, showing a great degree of overlap; therefore, interneurons fall more along a spectrum rather than into distinct subgroups. Although this group is very diverse, axonal arbo‐ rization and the downstream target domain plays a major role in classification and can reveal a lot about a circuitry's function. Essentially, where and how an interneuron synapses onto a target cell ultimately effects neuronal output and therefore function [61], is an essential ques‐ tion for cortical function. Interneurons are crucial for synchronizing and shaping the excitatory activity of pyramidal cells to form a 'task‐specific microcircuit' for a particular brain region [61]; the prefrontal cortex contains this microcircuit specialized for working memory [62].

Three common GABAergic neocortical interneurons that will be highlighted and addressed in this chapter are neurochemically defined based on the calcium‐binding proteins they express: calbindin (CB), calretinin (CR), and parvalbumin (PV) neurons. Calbindin interneu‐ rons (also referred to as somatostatin) makeup ~30% of the cortical interneuronal population and are generally characterized as having either small basket or Martinotti morphology. Commonly, small basket cells target proximal dendrites or the cell soma and electrophysi‐ ologically display regular‐spiking non‐pyramidal (RSNP) activity. Martinotti interneurons exhibit a burst‐spiking non‐pyramidal (BSNP) firing phenotype and target distal dendrites. Calretinin interneurons are the least prevalent (~15%) and stereotypically have small bipolar morphology. These interneurons target proximal dendrites and also other GABAergic inter‐ neurons having either RSNP or BSNP firing. Parvalbumin interneurons are fast‐spiking cells and neurochemically the largest group, making up half of the interneuronal population in the cortex. PV interneurons target all along a pyramidal cell, with large basket cells at the proximal dendrites/soma, nest cells at the soma, and chandelier cells targeting the axon initial segment. For the remainder of this section, we will focus on parvalbumin chandelier cells The Convergence of Glutamate and GABA Dysregulation in Schizophrenia http://dx.doi.org/10.5772/65870 11

to disinhibition of pyramidal neurons and excessive firing within the cortico‐limbic circuit. Physiologically, the excitotoxicity could have multiple effects on circuitry such as changes in membrane potential, receptor desensitization, or cell death. These results would have a twofold effect; first, the GABAergic downregulation would lead to negative symptoms and cognitive deficits. And second, the resulting excess glutamate release of cortico‐pyramidal neurons could activate dopaminergic systems that lead to positive symptoms and further cognitive impairments. The glutamate‐GABA systems in the forebrain, especially prefrontal cortex, are intertwined to produce prefrontal‐dependent cognitive function, as proposed in **Figure 3**. Still, how these two systems interact to induce phenotypes and symptoms in schizo‐

Cortical interneurons were first documented with Golgi staining by Santiago Ramón y Cajal and referred to as the "cells with short axons" [60]. Cortical interneurons are typically distin‐ guished by four common attributes: locally projecting, aspiny or sparsely spiny dendrites, small cell soma, and GABAergic. Interneurons exhibit a large diversity and are categorized based on several features including morphology, connectivity, neurochemistry, and physiology [60–62] (**Figure 4**). Due to the heterogeneity of this neuronal population, interneurons can fall into more than one category, showing a great degree of overlap; therefore, interneurons fall more along a spectrum rather than into distinct subgroups. Although this group is very diverse, axonal arbo‐ rization and the downstream target domain plays a major role in classification and can reveal a lot about a circuitry's function. Essentially, where and how an interneuron synapses onto a target cell ultimately effects neuronal output and therefore function [61], is an essential ques‐ tion for cortical function. Interneurons are crucial for synchronizing and shaping the excitatory activity of pyramidal cells to form a 'task‐specific microcircuit' for a particular brain region [61];

the prefrontal cortex contains this microcircuit specialized for working memory [62].

Three common GABAergic neocortical interneurons that will be highlighted and addressed in this chapter are neurochemically defined based on the calcium‐binding proteins they express: calbindin (CB), calretinin (CR), and parvalbumin (PV) neurons. Calbindin interneu‐ rons (also referred to as somatostatin) makeup ~30% of the cortical interneuronal population and are generally characterized as having either small basket or Martinotti morphology. Commonly, small basket cells target proximal dendrites or the cell soma and electrophysi‐ ologically display regular‐spiking non‐pyramidal (RSNP) activity. Martinotti interneurons exhibit a burst‐spiking non‐pyramidal (BSNP) firing phenotype and target distal dendrites. Calretinin interneurons are the least prevalent (~15%) and stereotypically have small bipolar morphology. These interneurons target proximal dendrites and also other GABAergic inter‐ neurons having either RSNP or BSNP firing. Parvalbumin interneurons are fast‐spiking cells and neurochemically the largest group, making up half of the interneuronal population in the cortex. PV interneurons target all along a pyramidal cell, with large basket cells at the proximal dendrites/soma, nest cells at the soma, and chandelier cells targeting the axon initial segment. For the remainder of this section, we will focus on parvalbumin chandelier cells

phrenia remains to be determined.

10 Schizophrenia Treatment - The New Facets

**11. GABAergic cortical interneurons**

**Figure 4.** Cortical interneuron connectivity and firing patterns categorized by calcium‐binding neurochemical markers. Calretinin small bipolar cells target proximal dendrites and other GABAergic interneurons. Calbindin neurons, small basket cells, and Martinotti cells, target proximal dendrites/soma and distal dendrites. Parvalbumin interneurons are fast‐spiking and are further classified into large basket, nest basket, and chandelier (Ch) cells. Large basket cells target proximal dendrites and the soma. Nest basket cells target the cell soma and chandelier cells synapse on the axon initial segment (Modified from Lewis et al. [62]).

since these are the interneurons known to play a major role in prefrontal cortex‐dependent working memory and also have been implicated in the pathophysiology of neuropsychiatric disorders such as schizophrenia [60, 62].
