Revisiting enigmatic cortical calretinin-expressing interneurons

Abstract

Cortical calretinin (CR)-expressing interneurons represent a heterogeneous subpopulation of about 10–30% of GABAergic interneurons, which altogether total ca. 12–20% of all cortical neurons. In the rodent neocortex, CR cells display different somatodendritic morphologies ranging from bipolar to multipolar but the bipolar cells and their variations dominate. They are also diverse at the molecular level as they were shown to express numerous neuropeptides in different combinations including vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), neurokinin B (NKB) corticotrophin releasing factor (CRF), enkephalin (Enk) but also neuropeptide Y (NPY) and somatostatin (SOM) to a lesser extent. CR-expressing interneurons exhibit different firing behaviors such as adapting, bursting or irregular. They mainly originate from the caudal ganglionic eminence (CGE) but a subpopulation also derives from the dorsal part of the medial ganglionic eminence (MGE). Cortical GABAergic CR-expressing interneurons can be divided in two main populations: VIP-bipolar interneurons deriving from the CGE and SOM-Martinotti-like interneurons originating in the dorsal MGE. Although bipolar cells account for the majority of CR-expressing interneurons, the roles they play in cortical neuronal circuits and in the more general metabolic physiology of the brain remained elusive and enigmatic. The aim of this review is, firstly, to provide a comprehensive view of the morphological, molecular and electrophysiological features defining this cell type. We will, secondly, also summarize what is known about their place in the cortical circuit, their modulation by subcortical afferents and the functional roles they might play in neuronal processing and energy metabolism.

GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits

“…Subtle differences among Vip INs with vertically oriented dendrites have been described. Some are bitufted, while others are single tufted, bipolar or tripolar (Bayraktar et al, 2000; Cauli et al, 2014). However, it is not clear that these differences in dendritic morphology are physiologically significant since they tend to sample similar intracolumnar and translaminar sectors.…”

“…Subpopulations of Vip neurons express molecular markers that may help in subdividing this group of INs (see table I) (Cauli et al, 2014; Ferezou et al, 2007; Taki et al, 2000). About 10–30 % of Vip INs express Cck and about 50–70% of Vip INs express CR.…”

“…Some Vip INs also express the ACh synthetizing enzyme choline acetyl transferase (ChAT). ChAT-expressing INs appear to be irregular spiking, CR+, and have “bipolar” dendritic morphology (Cauli et al, 2014; Porter et al, 1998). However, the cholinergic nature of these neurons is not clear.…”

Cotransmission of acetylcholine and GABA

“…These ChAT-expressing cells express the vasointestinal peptide (VIP), a common marker for a subclass of cortical interneuron, and share similar stereotyped morphology and laminar distribution (Consonni et al, 2009; Cauli et al, 2014). Only one study to date has attempted to directly address the function of these neurons, using paired recordings between cortical ChAT-expressing cells and neighboring pyramidal neurons (von Engelhardt et al, 2007).…”

“…However, the specialized functions of each ACh-releasing population are largely unknown. In the cerebral cortex, ACh is released from long-range axons projecting from basal forebrain neurons (Jones, 2004), with a potential contribution from local cholinergic interneurons (von Engelhardt et al, 2007; Consonni et al, 2009; Cauli et al, 2014). Like the cortex, the striatum has both local cholinergic interneurons and long-distance innervation from the brainstem cholinergic centers (Calabresi et al, 2000).…”