Pyramidal Neurons In Layer Research Articles

Aging-Related Alterations to Persistent Firing in the Lateral Entorhinal Cortex Contribute to Deficits in Temporal Associative Memory.

With aging comes a myriad of different disorders, and cognitive decline is one of them. Studies have consistently shown a decline amongst aged subjects in their ability to acquire and maintain temporal associative memory. Defined as the memory of the association between two objects that are separated in time, temporal associative memory is dependent on neocortical structures such as the prefrontal cortex and temporal lobe structures. For this memory to be acquired, a mental trace of the first stimulus is necessary to bridge the temporal gap so the two stimuli can be properly associated. Persistent firing, the ability of the neuron to continue to fire action potentials even after the termination of a triggering stimulus, is one mechanism that is posited to support this mental trace. A recent study demonstrated a decline in persistent firing ability in pyramidal neurons of layer III of the lateral entorhinal cortex with aging, contributing to learning impairments in temporal associative memory acquisition. In this work, we explore the potential ways persistent firing in lateral entorhinal cortex (LEC) III supports temporal associative memory, and how aging may disrupt this mechanism within the temporal lobe system, resulting in impairment in this crucial behavior.

Human Neocortex Layer Features Evaluated by PIXE, STIM, and STXM Techniques.

The human neocortex has a cytoarchitecture composed of six layers with an intrinsic organization that relates to afferent and efferent pathways for a high functional specialization. Various histological, neurochemical, and connectional techniques have been used to study these cortical layers. Here, we explore the additional possibilities of swift ion beam and synchrotron radiation techniques to distinguish cellular layers based on the elemental distributions and areal density pattern in the human neocortex. Temporal cortex samples were obtained from two neurologically normal adult men (postmortem interval: 6-12h). A cortical area of 500 × 500 μm2 was scanned by a 3MeV proton beam for elemental composition and areal density measurements using particle induced x-ray emission (PIXE) and scanning transmission ion microscopy (STIM), respectively. Zinc showed higher values in cortical layers II and V, which needs a critical discussion. Furthermore, the areal density decreased in regions with a higher density of pyramidal neurons in layers III and V. Scanning transmission X-ray microscopy (STXM) revealed the cellular density with higher lateral resolution than STIM, but not enough to distinguish each cortical lamination border. Our data describe the practical results of these approaches employing both X-ray and ion-beam based techniques for the human cerebral cortex and its heterogeneous layers. These results add to the potential approaches and knowledge of the human neocortical gray matter in normal tissue to develop improvements and address further studies on pathological conditions.

A Novel Layer 4 Corticofugal Cell Type/Projection Involved in Thalamo-Cortico-Striatal Sensory Processing

In sensory cortices, the information flow has been thought to be processed vertically across cortical layers, with layer 4 being the major thalamo-recipient which relays thalamic signals to layer 2/3, which in turn transmits thalamic information to layer 5 and 6 to then leave the cortex to reach subcortical and cortical long-range structures. Although several exceptions to this model have been described, neurons in layer 4 are still considered to establish only local (i.e., interlaminar and short-range) connections. Here, taking advantage of anatomic, electrophysiological, and optogenetic techniques, we describe, for the first time, a long-range corticostriatal class of pyramidal neurons in layer 4 (CS-L4) of the mouse auditory cortex that receive direct thalamic inputs. The CS-L4 neurons are embedded in a feedforward inhibitory circuit involving local parvalbumin neurons and establish connections in the posterior striatum in yet another feedforward inhibitory thalamo→cortico(L4)→striatal circuit which potentially contributes in controlling control the output of striatal spiny projection neurons.SIGNIFICANCE STATEMENTThe assumption has been that layer 4 neurons are the main thalamic recipient layer, projecting to the upper cortical layer 2/3. However, no study has revealed a detailed understanding of the circuit mechanisms by which layer 4 sends a projection to a subcortical structure, such as the striatum, and differentially innervate the spiny projection neurons (SPNs) and intrastriatal parvalbumin-expressing neurons. For the first time, our results demonstrate that the auditory cortex projects to the posterior part of the dorsal striatum via pyramidal neurons located in layer 4 (CS-L4 neurons). Here we propose a new wiring diagram that implemented the old one, in which layer 4 is not only involved in the transfer of thalamic input to the upper layer 2/3, but can also exert a direct top-down control, bypassing intracortical processing of subcortical structures, such as the posterior part of the dorsal striatum. This poses a new conceptual cell element (CS-L4 neurons) for experimental and theoretical work of the cortical function.

Microglia-triggered hypoexcitability plasticity of pyramidal neurons in the rat medial prefrontal cortex

Lipopolysaccharide (LPS), an outer component of Gram-negative bacteria, induces a strong response of innate immunity via microglia, which triggers a modulation of the intrinsic excitability of neurons. However, it is unclear whether the modulation of neurophysiological properties is similar among neurons. Here, we found the hypoexcitability of layer 5 (L5) pyramidal neurons after exposure to LPS in the medial prefrontal cortex (mPFC) of juvenile rats. We recorded the firing frequency of L5 pyramidal neurons long-lastingly under in vitro whole-cell patch-clamp, and we found a reduction of the firing frequency after applying LPS. A decrease in the intrinsic excitability against LPS-exposure was also found in L2/3 pyramidal neurons but not in fast-spiking interneurons. The decrease in the excitability by immune-activation was underlain by increased activity of small-conductance Ca2+-activated K+ channels (SK channels) in the pyramidal neurons and tumor necrosis factor (TNF)-α released from microglia. We revealed that the reduction of the firing frequency of L5 pyramidal neurons was dependent on intraneuronal Ca2+ and PP2B. These results suggest the hypoexcitability of pyramidal neurons caused by the upregulation of SK channels via Ca2+-dependent phosphatase during acute inflammation in the mPFC. Such a mechanism is in contrast to that of cerebellar Purkinje cells, in which immune activation induces hyperexcitability via downregulation of SK channels. Further, a decrease in the frequency of spontaneous inhibitory synaptic transmission reflected network hypoactivity. Therefore, our results suggest that the directionality of the intrinsic plasticity by microglia is not consistent, depending on the brain region and the cell type.

Local Connections of Pyramidal Neurons to Parvalbumin-Producing Interneurons in Motor-Associated Cortical Areas of Mice.

Parvalbumin (PV)-producing neurons are the largest subpopulation of cortical GABAergic interneurons, which mediate lateral, feedforward, and feedback inhibition in local circuits and modulate the activity of pyramidal neurons. Clarifying the specific connectivity between pyramidal and PV neurons is essential for understanding the role of PV neurons in local circuits. In the present study, we visualized somas and dendrites of PV neurons using transgenic mice in which PV neurons specifically express membrane-targeted GFP, and intracellularly labeled local axons of 26 pyramidal neurons in layers 2–6 in acute slices of the motor-associated cortex from transgenic mice. We mapped morphologically distribution of inputs from a pyramidal neuron to PV neurons based on contact sites (appositions) between the axons from an intracellularly filled pyramidal neuron and the dendrites of PV neurons. Layer 6 corticothalamic (CT)-like pyramidal neurons formed appositions to PV neurons at a significantly higher rate than other pyramidal neurons. The percentage of apposed varicosities to all the labeled varicosities of layer 6 CT-like neurons was 28%, and that of the other pyramidal neurons was 12–19%. Layer 6 CT-like neurons preferentially formed appositions with PV neurons in layers 5b–6, while other pyramidal neurons uniformly formed appositions with PV neurons in all layers. Furthermore, both layer 6 CT-like and corticocortical-like neurons more frequently formed compound appositions, where two or more appositions were located on a dendritic branch, than other pyramidal neurons. Layer 6 CT neurons may contribute to intracortical information processing through preferential connections with PV neurons in layers 5b–6.

Representational 'touch' and modulatory 'retouch'-two necessary neurobiological processes in thalamocortical interaction for conscious experience.

Theories of consciousness using neurobiological data or being influenced by these data have been focused either on states of consciousness or contents of consciousness. These theories have occasionally used evidence from psychophysical phenomena where conscious experience is a dependent experimental variable. However, systematic catalog of many such relevant phenomena has not been offered in terms of these theories. In the perceptual retouch theory of thalamocortical interaction, recently developed to become a blend with the dendritic integration theory, consciousness states and contents of consciousness are explained by the same mechanism. This general-purpose mechanism has modulation of the cortical layer-5 pyramidal neurons that represent contents of consciousness as its core. As a surplus, many experimental psychophysical phenomena of conscious perception can be explained by the workings of this mechanism. Historical origins and current views inherent in this theory are presented and reviewed.

Reduced number of satellite oligodendrocytes of pyramidal neurons in layer 5 of the prefrontal cortex in schizophrenia.

Neuroimaging, genetic and molecular biological studies have shown impaired intra-cortical myelination in patients with schizophrenia, particularly in the prefrontal cortex. Previously we reported a significant deficit of oligodendrocytes and oligodendrocyte clusters in layers 3 and 5 of the prefrontal cortex, Brodmann area 10 (BA10) in schizophrenia. In this current study, we investigate the number of oligodendrocyte satellites (Sat-Ol) per pyramidal neuron in layer 5 of BA10 in schizophrenia (n = 17) as compared to healthy controls (n = 20) in the same section collection as previously used to study the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters. We find a significant reduction (-39%, p < 0.001) in the number of Sat-Ol per neuron in schizophrenia as compared to the control group. The number of Sat-Ol per neuron did not correlate with the Nv of oligodendrocytes or with the Nv of oligodendrocyte clusters. Our previous studies of the inferior parietal lobule (BA39 and BA40), demonstrated significant decrease of the number of Sat-Ol only in patient subgroups with poor and fair insight. Additionally, correlation pattern between number of Sat-Ol and Nv of oligodendrocytes and oligodendrocyte clusters was similar between the two functionally interconnected cortical areas, BA10 and BA40, whereas in BA39, strong significant correlations were revealed between the number of Sat-Ol and Nv of oligodendrocyte clusters (0.9 ≤ R ≥ 0.66; p < 0.001). These data suggest that that specific features of Sat-Ol alterations patterns may be associated with specific activity-driven plasticity of corresponding networks in the brain of people with schizophrenia.

Changes in dendritic arborization related to the estrous cycle in pyramidal neurons of layer V of the motor cortex

Many studies on neuronal plasticity have been conducted in the hippocampus and sensory cortices. In female rats in the estrus phase, when there is a low concentration of estradiol in the blood, there is a reduction in the dendritic spine density of CA1 neurons, while an increase in dendritic spines has been observed during metestrus, when progesterone levels are high. In comparison with the hippocampus, less information is known about dendritic remodeling of the motor cortex. Thus, the objective of the present study was to evaluate the neuronal morphology of pyramidal cells of layer V of the motor cortex in each phase of the estrous cycle. For this, we used Long-Evans strain rats and formed 4 experimental groups according to the phase of the estrous cycle at the moment of sacrifice: proestrus, estrus, metestrus, or diestrus. All animals were gently monitored regarding the expression of one estrous cycle in order to determine the regularity of the cycle. We obtained the brains in order to evaluate the neuronal morphology of neurons of layer V of the primary motor cortex following the Golgi-Cox method and Sholl analysis. Our results show that the dendritic arborization of neurons of rats sacrificed in the metestrus phase is reduced compared to the other phases of the estrous cycle. However, we did not find changes in dendritic spine density between experimental groups. When comparing our results with previous data, we can suggest that estrogens and progesterone differentially promote plasticity events in pyramidal neurons between different brain regions.

Dissecting the neural underpinnings of the short-latency response to transcranial magnetic stimulation of motor cortex: A computational modeling study

Abstract Objective: Transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) elicits a series of high frequency volleys termed D- and I-waves measured epidurally in the corticospinal tract of awake humans. The D-wave is thought to be caused by direct activation of corticospinal axons, while I-waves are believed to be generated by trans-synaptic activation of corticospinal axons. The cortical circuits and mechanisms involved in the generation of I-waves by TMS of M1 remain unclear. Methods: We implemented a computational model of a cortical column with biophysically-based cortical neurons, following an existing model (Traub 2005). The TMS induced E-field was modeled as intracellular current injections of monophasic TMS pulses into the axon terminals of pyramidal neurons (PN). We constructed dose–response curves of spiking activity averaged across layer 5 (L5) PN as a function of the proportion of activated PN. Results: Model-based responses were compared to I-waves recorded from L5 PN in rodent M1 during TMS (Li 2017), and the network model reproduced I-waves only during the activation of axon terminals of L5 PN in contrast to activation of axon terminals of L2/3 or L6 PN. Inhibitory interneurons in deep layers fired in synchrony during the late phases of I-waves offering a potential explanation for the reduction in magnitude of late I-waves seen in experimental studies after administration of GABA-A agonists. Virtual lesioning of model neurons revealed that recurrent synaptic connections between L5 PN mediated by AMPA receptors play a prominent role in the generation of I-waves. Conclusions: Activation of presynaptic terminal of L5 PN is necessary to generate an I-wave response to TMS. Further, recurrent excitatory synaptic connections between L5 PN play a prominent role in the generation of I-wave response. Significance: Gaining a better understanding of circuit mechanisms of TMS of the M1 could enable optimization of stimulation paradigms. Keywords: Transcranial magnetic stimulation, I-waves, Cortical column model, Motor cortex

Reduced Synaptic Transmission and Intrinsic Excitability of a Subtype of Pyramidal Neurons in the Medial Prefrontal Cortex in a Mouse Model of Alzheimer's Disease.

Abnormal morphology and function of neurons in the prefrontal cortex (PFC) are associated with cognitive deficits in rodent models of Alzheimer's disease (AD), particularly in cortical layer-5 pyramidal neurons that integrate inputs from different sources and project outputs to cortical or subcortical structures. Pyramidal neurons in layer-5 of the PFC can be classified as two subtypes depending on the inducibility of prominent hyperpolarization-activated cation currents (h-current). However, the differences in the neurophysiological alterations between these two subtypes in rodent models of AD remain poorly understood. To investigate the neurophysiological alterations between two subtypes of pyramidal neurons in hAPP-J20 mice, a transgenic model for early onset AD. The synaptic transmission and intrinsic excitability of pyramidal neurons were investigated using whole-cell patch recordings. The morphological complexity of pyramidal neurons was detected by biocytin labelling and subsequent Sholl analysis. We found reduced synaptic transmission and intrinsic excitability of the prominent h-current (PH) cells but not the non-PH cells in hAPP-J20 mice. Furthermore, the function of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which mediated h-current was disrupted in the PH cells of hAPP-J20 mice. Sholl analysis revealed that PH cells had less dendritic intersections in hAPP-J20 mice comparing to control mice, implying that a lower morphological complexity might contribute to the reduced neuronal activity. These results suggest that the PH cells in the medial PFC may be more vulnerable to degeneration in hAPP-J20 mice and play a sustainable role in frontal dysfunction in AD.

IQSEC2 Deficiency Results in Abnormal Social Behaviors Relevant to Autism by Affecting Functions of Neural Circuits in the Medial Prefrontal Cortex.

IQSEC2 is a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factor 6 (Arf6), of which protein is exclusively localized to the postsynaptic density of the excitatory synapse. Human genome studies have revealed that the IQSEC2 gene is associated with X-linked neurodevelopmental disorders, such as intellectual disability (ID), epilepsy, and autism. In this study, we examined the behavior and synapse function in IQSEC2 knockout (KO) mice that we generated using CRIPSR/Cas9-mediated genome editing to solve the relevance between IQSEC2 deficiency and the pathophysiology of neurodevelopmental disorders. IQSEC2 KO mice exhibited autistic behaviors, such as overgrooming and social deficits. We identified that up-regulation of c-Fos expression in the medial prefrontal cortex (mPFC) induced by social stimulation was significantly attenuated in IQSEC2 KO mice. Whole cell electrophysiological recording identified that synaptic transmissions mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), N-methyl-D-aspartate receptor (NMDAR), and γ-aminobutyric acid receptor (GABAR) were significantly decreased in pyramidal neurons in layer 5 of the mPFC in IQSEC2 KO mice. Reexpression of IQSEC2 isoform 1 in the mPFC of IQSEC2 KO mice using adeno-associated virus (AAV) rescued both synaptic and social deficits, suggesting that impaired synaptic function in the mPFC is responsible for social deficits in IQSEC2 KO mice.

Serotonin Transporter Defect Disturbs Structure and Function of the Auditory Cortex in Mice.

Serotonin transporter (SERT) modulates the level of 5-HT and significantly affects the activity of serotonergic neurons in the central nervous system. The manipulation of SERT has lasting neurobiological and behavioral consequences, including developmental dysfunction, depression, and anxiety. Auditory disorders have been widely reported as the adverse events of these mental diseases. It is unclear how SERT impacts neuronal connections/interactions and what mechanism(s) may elicit the disruption of normal neural network functions in auditory cortex. In the present study, we report on the neuronal morphology and function of auditory cortex in SERT knockout (KO) mice. We show that the dendritic length of the fourth layer (L-IV) pyramidal neurons and the second-to-third layer (L-II/III) interneurons were reduced in the auditory cortex of the SERT KO mice. The number and density of dendritic spines of these neurons were significantly less than those of wild-type neurons. Also, the frequency-tonotopic organization of primary auditory cortex was disrupted in SERT KO mice. The auditory neurons of SERT KO mice exhibited border frequency tuning with high-intensity thresholds. These findings indicate that SERT plays a key role in development and functional maintenance of auditory cortical neurons. Auditory function should be examined when SERT is selected as a target in the treatment for psychiatric disorders.

Cytoarchitectonics of the Superior Parietal Cortex of an Outstanding Russian Scientist-Physiologist

The aim of the study is to identify possible cytoarchitectonic features of the structure of the cortex in the superior parietal region of an outstanding and talented scientist-physiologist.Material and methods. The cortex (area 7) of the superior parietal region of a scientist-physiologist and men of the senile age in the control group (8 hemispheres) was studied on the series of frontal brain slices, 20 μ thick, stained with cresyl purple according to Nissl method. The cortex area thickness, the thickness of the cytoarchitectonics layer III, the area of profile field of pyramidal neurons in layers III and V, the density of neurons surrounded by satellite glia and satellite glia density in layers III and V were measured in the cortex (area 7) of the superior parietal region in the left and right hemispheres of the brain.Results. We have identified several features of the cytoarchitectonics structure of the cortex (area 7) in the brain of the scientist-physiologist that may correlate with his outstanding scientific abilities. The cortex of a scientist-physiologist is characterized by a large thickness of the studied cortex and its cytoarchitectonic layers III and V, and a greater value of the area of the profile field of neurons if compared with the cortex in men of the senile age from the control group. A higher value of the neuron density and satellite glia in the cortex of the superior parietal region of the scientist-physiologist was revealed. There was also a lower severity of age-related changes in the cortex of the scientist-physiologist compared with the control group of men.Conclusion. The structure of the cortex (area 7) of the superior parietal region of the scientistphysiologist is characterized by a greater parameter of the cortical thickness and the thickness of the associative layer III, the size of neurons and the density of satellite glia if compared with those in men of the senile age of the control group. These features distinguish the structure of his cortex from the similar cortex of the control group of men and may be related to the features of the cognitive activity of the outstanding scientist-physiologist.

Long-term stability of cortical ensembles.

Neuronal ensembles, coactive groups of neurons found in spontaneous and evoked cortical activity, are causally related to memories and perception, but it is still unknown how stable or flexible they are over time. We used two-photon multiplane calcium imaging to track over weeks the activity of the same pyramidal neurons in layer 2/3 of the visual cortex from awake mice and recorded their spontaneous and visually evoked responses. Less than half of the neurons remained active across any two imaging sessions. These stable neurons formed ensembles that lasted weeks, but some ensembles were also transient and appeared only in one single session. Stable ensembles preserved most of their neurons for up to 46 days, our longest imaged period, and these 'core' cells had stronger functional connectivity. Our results demonstrate that neuronal ensembles can last for weeks and could, in principle, serve as a substrate for long-lasting representation of perceptual states or memories.

Risperidone Mitigates Enhanced Excitatory Neuronal Function and Repetitive Behavior Caused by an ASD-Associated Mutation of SIK1.

Six mutations in the salt-inducible kinase 1 (SIK1)-coding gene have been identified in patients with early infantile epileptic encephalopathy (EIEE-30) accompanied by autistic symptoms. Two of the mutations are non-sense mutations that truncate the C-terminal region of SIK1. It has been shown that the C-terminal-truncated form of SIK1 protein affects the subcellular distribution of SIK1 protein, tempting to speculate the relevance to the pathophysiology of the disorders. We generated SIK1-mutant (SIK1-MT) mice recapitulating the C-terminal-truncated mutations using CRISPR/Cas9-mediated genome editing. SIK1-MT protein was distributed in the nucleus and cytoplasm, whereas the distribution of wild-type SIK1 was restricted to the nucleus. We found the disruption of excitatory and inhibitory (E/I) synaptic balance due to an increase in excitatory synaptic transmission and enhancement of neural excitability in the pyramidal neurons in layer 5 of the medial prefrontal cortex in SIK1-MT mice. We also found the increased repetitive behavior and social behavioral deficits in SIK1-MT mice. The risperidone administration attenuated the neural excitability and excitatory synaptic transmission, but the disrupted E/I synaptic balance was unchanged, because it also reduced the inhibitory synaptic transmission. Risperidone also eliminated the repetitive behavior but not social behavioral deficits. These results indicate that risperidone has a role in decreasing neuronal excitability and excitatory synapses, ameliorating repetitive behavior in the SIK1-truncated mice.

High-frequency repetitive transcranial magnetic stimulation enhances layer II/III morphological dendritic plasticity in mouse primary motor cortex

High-frequency repeated transcranial magnetic stimulation (HF-rTMS) is a safe non-invasive neuromodulatory technique and there is a body of evidence shows that it can modulate plasticity in different brain areas. One of the most interesting application of HF-rTMS is the modulation of plasticity in primary motor cortex (M1) to promote recovery after brain injuries. However, the underlying mechanism by which HF-rTMS modulates motor cortex plasticity remain to be investigated.In this study, we investigated the effects of HF-rTMS treatment on morphological plasticity of pyramidal neurons in layer II/III (L2/3) of the primary motor cortex in mice. Our results show that the treatment did not increase anxiety in mice in the open field test and the elevated plus-maze test. Treated mice displayed increased total spine density in apical and basal dendrites, with a predominance of thin spines. The treatment also increased dendritic complexity, as assessed by Sholl analysis at both apical and basal dendrites.Collectively, the results show that HF-rTMS induced remarkable changes in dendritic complexity in primary motor cortex L2/3 connections which may strengthen corticocortical connections increasing integration of information across cortical areas. The data support the use of HF-rTMS as a circuit-targeting neuromodulation strategy.

Astrocytes control the spiking of mouse visual cortex layer 5 pyramidal neurons.

Astrocytes control the spiking of mouse visual cortex layer 5 pyramidal neurons.

Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice.

Astrocytes are integral components of synaptic transmission, and their dysfunction leads to neuropsychiatric disorders such as anxiety and depression. Liver X receptor β (LXRβ) is expressed in astrocytes, and LXRβ global knockout mice showsimpaired synaptic formation. In order to define the role of LXRβ in astrocytes, we used a conditional Cre-loxP system to specifically remove LXRβ from astrocytes. We found that this deletion caused anxiety-like but not depressive-like behaviors in adult male mice. This behavioral phenotype could be completely reproduced by selective deletion of LXRβ in astrocytes in the medial prefrontal cortex (mPFC). Pyramidal neurons in layer V of mPFC are involved in mood behaviors. We found that there was an increased spontaneous excitatory synaptic transmission in layer V pyramidal neurons of the mPFC of these mice. This was concurrent with increased dendritic complexity, despite normal appearance and number of dendritic spines. In addition, gene ontology analysis of RNA sequencing revealed that deletion of astrocytic LXRβ led to the enrichment of the process of synaptic transmission in mPFC. Finally, we also confirmed that renormalized excitatory synaptic transmission in layer V pyramidal neurons alleviated the anxiety in mice with astrocytic LXRβ deletion in mPFC. Together, our findings reveal that astrocytic LXRβ in mPFC is critical in the regulation of synaptic transmission, and this provides a potential new target for treatment of anxiety-like behavior.

Prefrontal Cortical Alterations of Actin Regulation and Energy Production in Layer 3 Pyramidal Neurons in Schizophrenia

Working memory, the ability to transiently maintain and manipulate a limited amount of information to guide thought or behavior, is impaired in schizophrenia. This impairment has been suggested to stem from hypoactive glutamatergic pyramidal neurons in layer 3 (L3PNs) of the dorsolateral prefrontal cortex (DLPFC). In schizophrenia, L3PNs exhibit morphological abnormalities such as smaller somal sizes, shorter dendritic arbors, and fewer dendritic spines, features that are all regulated by actin dynamics.

The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain.

Human cortical and subcortical areas integrate emotion, memory, and cognition when interpreting various environmental stimuli for the elaboration of complex, evolved social behaviors. Pyramidal neurons occur in developed phylogenetic areas advancing along with the allocortex to represent 70–85% of the neocortical gray matter. Here, we illustrate and discuss morphological features of heterogeneous spiny pyramidal neurons emerging from specific amygdaloid nuclei, in CA3 and CA1 hippocampal regions, and in neocortical layers II/III and V of the anterolateral temporal lobe in humans. Three-dimensional images of Golgi-impregnated neurons were obtained using an algorithm for the visualization of the cell body, dendritic length, branching pattern, and pleomorphic dendritic spines, which are specialized plastic postsynaptic units for most excitatory inputs. We demonstrate the emergence and development of human pyramidal neurons in the cortical and basomedial (but not the medial, MeA) nuclei of the amygdala with cells showing a triangular cell body shape, basal branched dendrites, and a short apical shaft with proximal ramifications as “pyramidal-like” neurons. Basomedial neurons also have a long and distally ramified apical dendrite not oriented to the pial surface. These neurons are at the beginning of the allocortex and the limbic lobe. “Pyramidal-like” to “classic” pyramidal neurons with laminar organization advance from the CA3 to the CA1 hippocampal regions. These cells have basal and apical dendrites with specific receptive synaptic domains and several spines. Neocortical pyramidal neurons in layers II/III and V display heterogeneous dendritic branching patterns adapted to the space available and the afferent inputs of each brain area. Dendritic spines vary in their distribution, density, shapes, and sizes (classified as stubby/wide, thin, mushroom-like, ramified, transitional forms, “atypical” or complex forms, such as thorny excrescences in the MeA and CA3 hippocampal region). Spines were found isolated or intermingled, with evident particularities (e.g., an extraordinary density in long, deep CA1 pyramidal neurons), and some showing a spinule. We describe spiny pyramidal neurons considerably improving the connectional and processing complexity of the brain circuits. On the other hand, these cells have some vulnerabilities, as found in neurodegenerative Alzheimer’s disease and in temporal lobe epilepsy.