Development of Cortical Interneurons

Abstract

Inhibitory local circuit neurons (LCNs), often called interneurons, have vital roles in the development and function of cortical networks. Their inhibitory influences regulate both the excitability of cortical projection neurons on the level of individual cells, and the synchronous activity of projection neuron ensembles that appear to be a neural basis for major aspects of cognitive processing. Dysfunction of LCNs has been associated with neurological and psychiatric diseases, such as epilepsy, schizophrenia, and autism. Here we review progress in understanding LCN fate determination, their nonradial migration to the cortex, their maturation within the cortex, and the contribution of LCN dysfunction to neuropsychiatric disorders.

Modeling a model: Mouse genetics, 22q11.2 Deletion Syndrome, and disorders of cortical circuit development

“…The key post-mortem changes, particularly in the parvalbumin-expressing subset of GABAergic interneurons, appear to be most robust in frontal and cingulate association cortices (Beasley et al, 2002; Hashimoto et al, 2003; Volk et al, 2012); however, other regions have not yet been extensively analyzed. There is a great deal of additional speculation about the role of altered inhibitory interneurons and networks in ASD (Chu and Anderson, 2014; Marin, 2012; Rubenstein and Merzenich, 2003). Nevertheless, there is only one preliminary report, based upon observations in post-mortem material of two ASD subjects, that shows a decline in frequency of parvalbumin, presumed basket cell, GABAergic interneurons (Zikopoulos and Barbas, 2013).…”

“…Though limited, these observations are consistent with the cellular cortical pathology reported for ASD, ADHD and SCZ: neuronal as well as cortical hypotrophy with some laminar selectivity focused on layer 2/3, and local morphogenetic anomalies including PH. The role of presumed cortical projection neuron migratory anomalies like PH in ASD, ADHD and SCZ remains uncertain (for review see: Chu and Anderson, 2014; Marin, 2012; McManus and Golden, 2005). Nevertheless, disrupted migration is robustly associated with more severe developmental behavioral disorders, particularly intellectual disability (Liu, 2011), which is seen in some 22q11DS patients, either in isolation, or accompanying ASD, ADHD or SCZ related behavioral pathology (Jonas et al, 2014).…”

Neurodevelopment and the Origins of Brain Disorders

“…Specific gene families, implicated from the discovery of rare, causal mutations, are highlighted, as well as the ways in which genetic data may be useful for improving future diagnostic and treatment strategies. Chu and Anderson (2015) provide a basic framework for understanding the origins and development of neocortical interneurons. This topic is of particular importance because of the role of excitatory:inhibitory balance in cortical information processing, and its implication in many neurodevelopmental and psychiatric disorders.…”

Tyrosine hydroxylase-producing neurons in the human cerebral cortex do not colocalize with calcium-binding proteins or the serotonin 3A receptor

“…In the embryonic rodent cortex, projection neurons originate locally in the ventricular zone. Most interneurons, in contrast, are generated in subcortical forebrain sites, including the medial and caudal ganglionic eminences (MGE and CGE, respectively) and the preoptic area, and these cells then migrate into the developing cortex (Chu and Anderson, 2015; Gelman et al, 2009; Wonders and Anderson, 2006). A small subset of rodent interneurons appears to arise in the cortical subventricular zone (Inta et al, 2008).…”

“…Cortical interneurons are clinically relevant; their dysfunction has been implicated in a variety of neurological disorders, including schizophrenia and epilepsy (Benes and Berretta, 2001; Chu and Anderson, 2015; Daskalakis et al, 2007; Di Cristo, 2007; Levitt et al, 2004; Lewis et al, 2012; Marin, 2012). Diverse subgroups of interneurons have been identified on the basis of their morphology, electrophysiological characteristics, embryonic origin, and molecular and neurochemical attributes (Ascoli et al, 2008; Chu and Anderson, 2015; Vitalis and Rossier, 2011; Wonders and Anderson, 2006). In the rodent neocortex, three non-overlapping subsets of interneurons have been defined based on the production of the calcium-binding proteins parvalbumin (PV) or calretinin (CR) or the peptide somatostatin (SST) (Gonchar and Burkhalter, 1997; Kubota et al, 1994; Xu et al, 2004).…”