Abstract
From an anatomical point of view the neocortex is subdivided into up to six layers depending on the cortical area. This subdivision has been described already by Meynert and Brodmann in the late 19/early 20. century and is mainly based on cytoarchitectonic features such as the size and location of the pyramidal cell bodies. Hence, cortical lamination is originally an anatomical concept based on the distribution of excitatory neuron. However, it has become apparent in recent years that apart from the layer-specific differences in morphological features, many functional properties of neurons are also dependent on cortical layer or cell type. Such functional differences include changes in neuronal excitability and synaptic activity by neuromodulatory transmitters. Many of these neuromodulators are released from axonal afferents from subcortical brain regions while others are released intrinsically. In this review we aim to describe layer- and cell-type specific differences in the effects of neuromodulator receptors in excitatory neurons in layers 2–6 of different cortical areas. We will focus on the neuromodulator systems using adenosine, acetylcholine, dopamine, and orexin/hypocretin as examples because these neuromodulator systems show important differences in receptor type and distribution, mode of release and functional mechanisms and effects. We try to summarize how layer- and cell type-specific neuromodulation may affect synaptic signaling in cortical microcircuits.
Highlights
The notion that the neocortex is subdivided into six different laminae was first introduced around the middle of the 19th century and primarily based on its cytoarchitecture, i.e., the distribution and size of pyramidal cell bodies (Meynert, 1867; Brodmann, 1909) and myeloarchitecture, i.e., the projection pattern of long range, intracortical axon (Baillarger, 1840; Vogt, 1906; see von Economo, 1929)
It has been demonstrated that a number of genes exhibit a clear patterned expression delineating cortical layers
In another study a dual component nicotinic acetylcholine (ACh) receptor channels (nAChRs) response was recorded in L5 pyramidal cells of both frontal and somatosensory cortex that was mediated by both α7 and α4β2 receptors, with the latter becoming more prominent during prolonged ACh application (Zolles et al, 2009). These conflicting results may result from the fact that cholinergic EPSPs and whole cell responses are mediated by different nAChR subtypes as well as neocortical region-specific differences in the expression of nAChR subtypes. In both L6A and L6B pyramidal neurons, ACh application induces a very slowly desensitizing inward current indicating the presence of α4β2∗ nAChR combined with the accessory α5 subunit that further slows down receptor desensitization (Kassam et al, 2008; Alves et al, 2010; Bailey et al, 2012; Poorthuis et al, 2013a,b; Hay et al, 2015; see Sundberg et al, 2017)
Summary
The notion that the neocortex is subdivided into six different laminae was first introduced around the middle of the 19th century and primarily based on its cytoarchitecture, i.e., the distribution and size of pyramidal cell bodies (Meynert, 1867; Brodmann, 1909) and myeloarchitecture, i.e., the projection pattern of long range, intracortical axon (Baillarger, 1840; Vogt, 1906; see von Economo, 1929). We will mainly concentrate here on data from functional, mostly electrophysiological studies which allow a cell-specific examination of neuromodulator action and its underlying mechanisms such as the coupled G-Protein type and ion channel types activated via intracellular enzyme cascades as well as the coupled ionotropic nAChR channel subtypes. This data will be put in context with earlier in situ hybridisation, immunohistochemical, receptor autoradiography and electronmicroscopy studies whenever necessary or possible. It is a so-called membrane-delimited step because the β/γ-subunit complex diffuses over a short distance within the cell membrane (for reviews see Doupnik, 2008; Lüscher and Slesinger, 2010; Dascal and Kahanovitch, 2015; Zamponi et al, 2015; Huang and Zamponi, 2017)
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