| Excitatory neuron types in layers 2-6 of the (A) medial prefrontal and (B) primary somatosensory (barrel) cortex. Different excitatory neuron types in cortical layers 2-6 (L2-L6) of rat mPFC and S1 barrel cortex are shown. Most neuron types are pyramidal cells with apical dendrites of different shape and length with the exception of spiny stellate cells in layer 4 and multipolar neurons in layer 6B. Somatodendritic domains are shown in different shades of red, with bright red indicating superficial and dark red deep layers. Note that the diversity of excitatory neurons is much higher than that shown here and that even between e.g., sensory cortices different pyramidal cell types can be found. L2P: L2 pyramidal cell; L3stP: L3 slender-tufted pyramidal cell, L3btP: L3 broad-tufted pyramidal cell; L3P: L3 pyramidal cell; L4SSC: L4 spiny stellate cell; L4SP: L4 star pyramidal cell; L5stP: L5 slender-tufted pyramidal cell (with strong axonal projections to layer 2 and 3); L5utP: L5 untufted pyramidal cell; L5btP: L5 broad-tufted pyramidal cell and L5ttP: L5 thick-tufted pyramidal cell (both of which project mainly to subcortical targets); L6A tall P: L6A tall pyramidal cell; L6A wide P: L6A wide pyramidal cell; L6A invP: L6A inverted pyramidal cell; L6AccP: L6A corticocortical pyramidal cell; L6ActP: L6A corticothalamic pyramidal cellL6AP: L6BP L6B pyramidal cell; L6BMC: L6B multipolar cell. This terminology will be used throughout the remainder of the text. 

| Excitatory neuron types in layers 2-6 of the (A) medial prefrontal and (B) primary somatosensory (barrel) cortex. Different excitatory neuron types in cortical layers 2-6 (L2-L6) of rat mPFC and S1 barrel cortex are shown. Most neuron types are pyramidal cells with apical dendrites of different shape and length with the exception of spiny stellate cells in layer 4 and multipolar neurons in layer 6B. Somatodendritic domains are shown in different shades of red, with bright red indicating superficial and dark red deep layers. Note that the diversity of excitatory neurons is much higher than that shown here and that even between e.g., sensory cortices different pyramidal cell types can be found. L2P: L2 pyramidal cell; L3stP: L3 slender-tufted pyramidal cell, L3btP: L3 broad-tufted pyramidal cell; L3P: L3 pyramidal cell; L4SSC: L4 spiny stellate cell; L4SP: L4 star pyramidal cell; L5stP: L5 slender-tufted pyramidal cell (with strong axonal projections to layer 2 and 3); L5utP: L5 untufted pyramidal cell; L5btP: L5 broad-tufted pyramidal cell and L5ttP: L5 thick-tufted pyramidal cell (both of which project mainly to subcortical targets); L6A tall P: L6A tall pyramidal cell; L6A wide P: L6A wide pyramidal cell; L6A invP: L6A inverted pyramidal cell; L6AccP: L6A corticocortical pyramidal cell; L6ActP: L6A corticothalamic pyramidal cellL6AP: L6BP L6B pyramidal cell; L6BMC: L6B multipolar cell. This terminology will be used throughout the remainder of the text. 

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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 laminati...

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... Neuronal morphologies vary significantly across different regions of the neocortex (prefrontal, parietal, occipital), especially with respect to the shape of their axons. However, within the parietal cortex, and more specifically within nbS1, neuronal morphologies share similar properties due to the similarity of layer composition and cortical thickness (Radnikow and Feldmeyer, 2018;Scala et al., 2019). As a result, cell types and neuronal reconstructions extracted from the hindlimb region are suitable to populate the entire nbS1. ...
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... The mammalian forebrain is organized into loops connecting the cortex, thalamus, and basal ganglia (Foster and others 2021). Broadly, the cortex is largely composed of recurrent excitatory circuits (Peron and others 2020) arranged in layers (Radnikow and Feldmeyer 2018) that can maintain activity patterns across multiple time scales relevant to driving adaptive behavior, while local cortical interneurons gate and sculpt these activity patterns (Hu and others 2014). In relation to the cortex, the thalamus is a centrally located subcortical region divided into nuclei, which are primarily composed of excitatory neurons (Butler 2008;Hunnicutt and others 2014;Jones 2007). ...
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... These are known to have multiple effects, which in part depend on receptor distributions and substance concentration, likely to vary across neurons. Acetylcholine, for example, preferentially contributes to a facilitation of CT layer 6 neurons by an interaction of muscarinic and nicotinic receptors (in rats: Yang et al., 2020; and for recent reviews of neuromodulators: Coppola and Disney, 2018;Jacob and Nienborg, 2018;Radnikow and Feldmeyer, 2018). In primary somatosensory and visual cortices (but also non-primary sensory areas), orexin, a peptide associated with wakefulness and attention, excites cortical neurons in layer 6B by a direct postsynaptic action (rats: Bayer et al., 2004). ...
... In excitatory pyramidal neurons, the secreted TNF-α activates downward signaling of TNF-receptors and the intraneuronal PP2B (Pribiag and Stellwagen, 2013), while the molecular mechanism that microglia modulate the neuronal intrinsic excitability is unclear. The cerebral cortex includes different cell types, and their physiological and morphological properties have been characterized (Radnikow and Feldmeyer, 2018). We consider it beneficial and informative to reveal the mechanism of the immune-triggered plasticity in the cerebrum towards understanding certain disease models. ...
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... ACh effects are mediated by two different types of receptors, the G-protein-coupled muscarinic ACh receptors (mAChRs) and the ionotropic nicotinic ACh receptors (nAChRs). In the neocortex, both receptor types show layer-specific distributions and effects (Obermayer et al. 2017;Radnikow and Feldmeyer 2018). In general, ACh increases the excitability of pyramidal cells located in different cortical layers by activating both nAChRs and mAChRs (Gulledge et al. 2007;Zolles et al. 2009;Bailey et al. 2010;Tian et al. 2014;Hay et al. 2016;Yang et al. 2020;Patel et al. 2021). ...
Preprint
Full-text available
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... Second, L2/3 neurons in both species have smaller dendritic arbors (Rojo et al., 2016) (e.g., compared with dendritic arbors of layer 5 neurons), allowing analyses in limited-volume EM datasets of a larger fraction of all the synapses on a particular neuron. Third, there seems to be a limited number of morphological cell types in L2/3 (Gouwens et al., 2019;Radnikow and Feldmeyer, 2018;Wang et al., 2018), increasing the probability that our measurements reflect comparisons among similar cell types. ...
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Detailing how primate and mouse neurons differ is critical for creating generalized models of how neurons process information. We reconstruct 15,748 synapses in adult Rhesus macaques and mice and ask how connectivity differs on identified cell types in layer 2/3 of primary visual cortex. Primate excitatory and inhibitory neurons receive 2–5 times fewer excitatory and inhibitory synapses than similar mouse neurons. Primate excitatory neurons have lower excitatory-to-inhibitory (E/I) ratios than mouse but similar E/I ratios in inhibitory neurons. In both species, properties of inhibitory axons such as synapse size and frequency are unchanged, and inhibitory innervation of excitatory neurons is local and specific. Using artificial recurrent neural networks (RNNs) optimized for different cognitive tasks, we find that penalizing networks for creating and maintaining synapses, as opposed to neuronal firing, reduces the number of connections per node as the number of nodes increases, similar to primate neurons compared with mice.