Apical Dendrites Research Articles

HIV-1 Tat reduces apical dendritic spine density throughout the trisynaptic pathway in the hippocampus of male transgenic mice

Nearly one-third of persons infected with HIV-1 (PWH) develop HIV-associated neurocognitive disorders (HAND), which can be exacerbated by exposure to opioids. The impact of opioids on HIV-induced alterations in neuronal plasticity is less well understood. Both morphine exposure and HIV have been shown to disrupt synaptic growth and stability in the hippocampus suggesting a potential site of convergence for their deleterious effects. In the present study, we examined the density of dendritic spines in CA1 and CA3 pyramidal neurons, and granule neurons within the dentate gyrus representing the hippocampal trisynaptic pathway after short-term exposure to the HIV transactivator of transcription (Tat) protein and morphine. We exposed inducible male, HIV-1 Tat transgenic mice to escalating doses of morphine (10–40 mg/kg, b.i.d.) and examined synaptodendritic structure in Golgi-impregnated hippocampal neurons. HIV-1 Tat, but not morphine, systematically reduced the density of apical, but not basilar, dendrites of CA1 and CA3 pyramidal neurons, and granule neuronal apical dendrites, suggesting the coordinated loss of specific synaptic interconnections throughout the hippocampal trisynaptic pathway.

Neuropilin 2/Plexin-A3 Receptors Regulate the Functional Connectivity and the Excitability in the Layers 4 and 5 of the Cerebral Cortex.

The functions of cortical networks are progressively established during development by series of events shaping the neuronal connectivity. Synaptic elimination, which consists of removing the supernumerary connections generated during the earlier stages of cortical development, is one of the latest stages in neuronal network maturation. The semaphorin 3F coreceptors neuropilin 2 (Nrp2) and plexin-A3 (PlxnA3) may play an important role in the functional maturation of the cerebral cortex by regulating the excess dendritic spines on cortical excitatory neurons. Yet, the identity of the connections eliminated under the control of Nrp2/PlxnA3 signaling is debated, and the importance of this synaptic refinement for cortical functions remains poorly understood. Here, we show that Nrp2/PlxnA3 controls the spine densities in layer 4 (L4) and on the apical dendrite of L5 neurons of the sensory and motor cortices. Using a combination of neuroanatomical, ex vivo electrophysiology, and in vivo functional imaging techniques in Nrp2 and PlxnA3 KO mice of both sexes, we disprove the hypothesis that Nrp2/PlxnA3 signaling is required to maintain the ectopic thalamocortical connections observed during embryonic development. We also show that the absence of Nrp2/PlxnA3 signaling leads to the hyperexcitability and excessive synchronization of the neuronal activity in L5 and L4 neuronal networks, suggesting that this system could participate in the refinement of the recurrent corticocortical connectivity in those layers. Altogether, our results argue for a role of semaphorin-Nrp2/PlxnA3 signaling in the proper maturation and functional connectivity of the cerebral cortex, likely by controlling the refinement of recurrent corticocortical connections.SIGNIFICANCE STATEMENT The function of a neuronal circuit is mainly determined by the connections that neurons establish with one another during development. Understanding the mechanisms underlying the establishment of the functional connectivity is fundamental to comprehend how network functions are implemented, and to design treatments aiming at restoring damaged neuronal circuits. Here, we show that the cell surface receptors for the family of semaphorin guidance cues neuropilin 2 (Nrp2) and plexin-A3 (PlxnA3) play an important role in shaping the functional connectivity of the cerebral cortex likely by trimming the recurrent connections in layers 4 and 5. By removing the supernumerary inputs generated during early development, Nrp2/PlxnA3 signaling reduces the neuronal excitability and participates in the maturation of the cortical network functions.

Dual role of low frequency magnetic field on neuroinflammation induced dendritic trimming and memory impairment on rat model of sporadic Alzheimer’s disease

Gliosis and dendritic loss is reported to be secondary to the amyloid beta (Aß) and hyperphosphorylated tau (hp‐tau) production in Alzheimer’s disease(AD) brain. STZ administration is reported to induce sporadic AD. Previous clinical or preclinical studies on effect of rTMS treatment in AD patients or APP23 mice showed cognitive improvement alone or as adjuvant therapy along‐with amelioration of the glial aggravation in the hippocampus. However, studies on the effect of magnetic field stimulation on the gliosis related dendritic trimming in animal models of sporadic AD is elusive. Therefore, in the present study we have looked in to the effect of extremely low frequency magnetic field stimulation (ELF‐MF; 17.96µT, 50Hz, 2hr/day) for one month post‐injection of STZ (bilateral, 3mg/kg). Total 45 animals were (ethical no. 937/IAEC/2016) randomly divided into five groups: Control, Sham, AD, Sham+MF and AD+MF. After assessing retention of spatial and avoidance memory using Morris water maze and passive avoidance step down test on 30th day, animals were sacrificed and tissues processed for oxidative stress and immunofluorescence, Golgi‐Cox staining. Behavioural analysis revealed spatial memory improvement with no effect on the avoidance memory loss in AD+MF group as compared to AD group. We also found significant decrease in superoxide dismutase, catalase, GSH and increase in malon‐di‐aldehyde (MDA) in AD group. ELF‐MF treatment only reduced MDA level in hippocampus and frontal cortex. GFAP, IBA‐1 and hp‐tau (ser356) positive cells were found to be reduced in AD+MF group, as compared to all groups except Control. Sholl analysis revealed partial improvement of reduction in the number of intersection, bifurcation and length in basal and apical dendrite in the AD group after ELF‐MF treatment in CA3 layer. These findings suggests dual role of ELF‐MF exposure on STZ model of AD showing improvement of spatial memory by reducing the gliosis induced dendritic loss. However, inability to manage oxidative stress due to STZ, which may lead to avoidance memory deficit even after exposure period of one month.

REM sleep promotes bidirectional plasticity in developing visual cortex in vivo

Sleep is required for the full expression of plasticity during the visual critical period (CP). However, the precise role of rapid-eye-movement (REM) sleep in this process is undetermined. Previous studies in rodents indicate that REM sleep weakens cortical circuits following MD, but this has been explored in only one class of cortical neuron (layer 5 apical dendrites). We investigated the role of REM sleep in ocular dominance plasticity (ODP) in layer 2/3 neurons using 2-photon calcium imaging in awake CP mice. In contrast to findings in layer 5 neurons, we find that REM sleep promotes changes consistent with synaptic strengthening and weakening. This supports recent suggestions that the effects of sleep on plasticity are highly dependent upon the type of circuit and preceding waking experience.

Structural Analysis of Human and Mouse Dendritic Spines Reveals a Morphological Continuum and Differences across Ages and Species.

Dendritic spines have diverse morphologies, with a wide range of head and neck sizes, and these morphologic differences likely generate different functional properties. To explore how this morphologic diversity differs across species and ages we analyzed 3D confocal reconstructions of ∼8000 human spines and ∼1700 mouse spines, labeled by intracellular injections in fixed tissue. Using unsupervised algorithms, we computationally separated spine heads and necks and systematically measured morphologic features of spines in apical and basal dendrites from cortical pyramidal cells. Human spines had unimodal distributions of parameters, without any evidence of morphologic subtypes. Their spine necks were longer and thinner in apical than in basal spines, and spine head volumes of an 85-year-old individual were larger than those of a 40-year-old individual. Human spines had longer and thicker necks and larger head volumes than mouse spines. Our results indicate that human spines form part of a continuum, are larger and longer than those of mice, and become larger with increasing adult age. These morphologic differences in spines across species could generate functional differences in biochemical and electrical spine compartmentalization, or in synaptic properties, across species and ages.

General anesthesia globally synchronizes activity selectively in layer 5 cortical pyramidal neurons

SummaryGeneral anesthetics induce loss of consciousness, a global change in behavior. However, a corresponding global change in activity in the context of defined cortical cell types has not been identified. Here, we show that spontaneous activity of mouse layer 5 pyramidal neurons, but of no other cortical cell type, becomes consistently synchronized in vivo by different general anesthetics. This heightened neuronal synchrony is aperiodic, present across large distances, and absent in cortical neurons presynaptic to layer 5 pyramidal neurons. During the transition to and from anesthesia, changes in synchrony in layer 5 coincide with the loss and recovery of consciousness. Activity within both apical and basal dendrites is synchronous, but only basal dendrites’ activity is temporally locked to somatic activity. Given that layer 5 is a major cortical output, our results suggest that brain-wide synchrony in layer 5 pyramidal neurons may contribute to the loss of consciousness during general anesthesia.

Modular microcircuit organization of the presubicular head-direction map.

Our internal sense of direction is thought to rely on the activity of head-direction (HD) neurons. We find that the mouse dorsal presubiculum (PreS), a key structure in the cortical representation of HD, displays a modular "patch-matrix" organization, which is conserved across species (including human). Calbindin-positive layer 2 neurons within the "matrix" form modular recurrent microcircuits, while inputs from the anterodorsal and laterodorsal thalamic nuclei are non-overlapping and target the "patch" and "matrix" compartments, respectively. The apical dendrites of identified HD cells are largely restricted within the "matrix," pointing to a non-random sampling of patterned inputs and to a precise structure-function architecture. Optogenetic perturbation of modular recurrent microcircuits results in a drastic tonic suppression of firing only in a subpopulation of HD neurons. Altogether, our data reveal a modular microcircuit organization of the PreS HD map and point to the existence of cell-type-specific microcircuits that support the cortical HD representation.

Dynamic interplay between thalamic activity and Cajal-Retzius cells regulates the wiring of cortical layer 1.

SummaryCortical wiring relies on guidepost cells and activity-dependent processes that are thought to act sequentially. Here, we show that the construction of layer 1 (L1), a main site of top-down integration, is regulated by crosstalk between transient Cajal-Retzius cells (CRc) and spontaneous activity of the thalamus, a main driver of bottom-up information. While activity was known to regulate CRc migration and elimination, we found that prenatal spontaneous thalamic activity and NMDA receptors selectively control CRc early density, without affecting their demise. CRc density, in turn, regulates the distribution of upper layer interneurons and excitatory synapses, thereby drastically impairing the apical dendrite activity of output pyramidal neurons. In contrast, postnatal sensory-evoked activity had a limited impact on L1 and selectively perturbed basal dendrites synaptogenesis. Collectively, our study highlights a remarkable interplay between thalamic activity and CRc in L1 functional wiring, with major implications for our understanding of cortical development.

Microanatomical study of pyramidal neurons in the contralesional somatosensory cortex after experimental ischemic stroke.

At present, many studies support the notion that after stroke, remote regions connected to the infarcted area are also affected and may contribute to functional outcome. In the present study, we have analyzed possible microanatomical alterations in pyramidal neurons from the contralesional hemisphere after induced stroke. We performed intracellular injections of Lucifer yellow in pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere in an ischemic stroke mouse model. A detailed 3-dimensional analysis of the neuronal complexity and morphological alterations of dendritic spines was then performed. Our results demonstrate that pyramidal neurons from layer III in the somatosensory cortex of the contralesional hemisphere show selective changes in their dendritic arbors, namely, less dendritic complexity of the apical dendritic arbor-but no changes in the basal dendritic arbor. In addition, we found differences in spine morphology in both apical and basal dendrites comparing the contralesional hemisphere with the lesional hemisphere. Our results show that pyramidal neurons of remote areas connected to the infarct zone exhibit a series of selective changes in neuronal complexity and morphological distribution of dendritic spines, supporting the hypothesis that remote regions connected to the peri-infarcted area are also affected after stroke.

An Optimized and Detailed Step-by-Step Protocol for the Analysis of Neuronal Morphology in Golgi-Stained Fetal Sheep Brain

Antenatal brain development during the final trimester of human pregnancy is a time when mature neurons become increasingly complex in morphology, through axonal and dendritic outgrowth, dendritic branching, and synaptogenesis, together with myelin production. Characterizing neuronal morphological development over time is of interest to developmental neuroscience and provides the framework to measure gray matter pathology in pregnancy compromise. Neuronal microstructure can be assessed with Golgi staining, which selectively stains a small percentage (1–3%) of neurons and their entire dendritic arbor. Advanced imaging processing and analysis tools can then be employed to quantitate neuronal cytoarchitecture. Traditional Golgi-staining protocols have been optimized, and commercial kits are readily available offering improved speed and sensitivity of Golgi staining to produce consistent results. Golgi-stained tissue is then visualized under light microscopy and image analysis may be completed with several software programs for morphological analysis of neurons, including freeware and commercial products. Each program requires optimization, whether semiautomated or automated, requiring different levels of investigator intervention and interpretation, which is a critical consideration for unbiased analysis. Detailed protocols for fetal ovine brain tissue are lacking, and therefore, we provide a step-by-step workflow of computer software analysis for morphometric quantification of Golgi-stained neurons. Here, we utilized the commonly applied FD Rapid GolgiStain kit (FD NeuroTechnologies) on ovine fetal brains collected at 127 days (0.85) of gestational age for the analysis of CA1 pyramidal neurons in the hippocampus. We describe the step-by-step protocol to retrieve neuronal morphometrics using Imaris imaging software to provide quantification of apical and basal dendrites for measures of dendrite length (μm), branch number, branch order, and Sholl analysis (intersections over radius). We also detail software add-ons for data retrieval of dendritic spines including the number of spines, spine density, and spine classification, which are critical indicators of synaptic function. The assessment of neuronal morphology in the developing brain using Rapid-Golgi and Imaris software is labor-intensive, particularly during the optimization period. The methodology described in this step-by-step description is novel, detailed, and aims to provide a reproducible, working protocol to quantify neuronal cytoarchitecture with simple descriptions that will save time for the next users of these commonly used techniques.

The passive properties of dendrites modulate the propagation of slowly-varying firing rate in feedforward networks

The propagation of slowly-varying firing rates has been proved significant for the development of the central nervous system. Recent reports have shown that the membrane passive properties of dendrites play a key role in the computation of the single neuron, which is of great importance to the function of neural networks. However, it is still unclear how dendritic passive properties affect the ability of cortical networks to propagate slowly-varying spiking activity. Here, we use two-compartment biophysical models to construct multilayered feedforward neural networks (FFNs) to investigate how dendritic passive properties affect the propagation of the slow-varying inputs. In the two-compartment biophysical models, one compartment represents apical dendrites, and the other compartment describes the soma plus the axon initial segment. Area proportion occupied by somatic compartment and coupling conductance between dendritic and somatic compartments are abstracted to capture the dendritic passive properties. A time-varying signal is injected into the first layer of the FFNs and the fidelity of the signal during propagation is used to qualify the ability of the FFN to transmit wave-like signals. Numerical results reveal an optimal value of coupling conductance between dendritic and somatic compartments to maximize the fidelity of the initial spiking activity. An increase of the dendritic area enhances the initial firing rate of neurons in the first layer by increasing the response of neurons to slow-varying wave-like input, resulting in a delay of attenuation of the firing rate, thus promoting the transmission of signals in FFN. Using a mean-field approach, we examine that changes in area proportion occupied by somatic compartment and coupling conductance between dendritic and somatic compartment affect the signal propagation ability of the FFN by adjusting the input–output transform of a single neuron. With the participation of external noise, a wide range of initial firing rates maintains a unique representation during propagation, which ensures the reliable transmission of slow-varying signals in FFNs. These findings are helpful to understand how passive properties of dendrites participate in the propagation of slowly varying signals in the cerebellum.

Semaphorin3A/PlexinA3 association with the Scribble scaffold for cGMP increase is required for apical dendrite development.

SUMMARYThe development of the apical dendrite from the leading process of the bipolar pyramidal neuron might be directed by spatially organized extrinsic cues acting on localized intrinsic determinants. The extracellular cues regulating apical dendrite polarization remain elusive. We show that leading process and apical dendrite development are directed by class III Semaphorins and mediated by a localized cGMP-synthesizing complex. The scaffolding protein Scribble that associates with the cGMP-synthesizing enzyme soluble guanylate cyclase (sGC) also associates with the Semaphorin3A (Sema3A) co-receptor PlexinA3. Deletion or knockdown of PlexinA3 and Sema3A or disruption of PlexinA3-Scribble association prevents Sema3A-mediated cGMP increase and causes defects in apical dendrite development. These manipulations also impair bipolar polarity and leading process establishment. Local cGMP elevation or sGC expression rescues the effects of PlexinA3 knockdown or PlexinA3-Scribble complex disruption. During neuronal polarization, leading process and apical dendrite development are directed by a scaffold that links Semaphorin cue to cGMP increase.

Frequency- and spike-timing-dependent mitochondrial Ca2+ signaling regulates the metabolic rate and synaptic efficacy in cortical neurons.

Mitochondrial activity is crucial for the plasticity of central synapses, but how the firing pattern of pre- and postsynaptic neurons affects the mitochondria remains elusive. We recorded changes in the fluorescence of cytosolic and mitochondrial Ca2+ indicators in cell bodies, axons, and dendrites of cortical pyramidal neurons in mouse brain slices while evoking pre- and postsynaptic spikes. Postsynaptic spike firing elicited fast mitochondrial Ca2+ responses that were about threefold larger in the somas and apical dendrites than in basal dendrites and axons. The amplitude of these responses and metabolic activity were extremely sensitive to the firing frequency. Furthermore, while an EPSP alone caused no detectable Ca2+ elevation in the dendritic mitochondria, the coincidence of EPSP with a backpropagating spike produced prominent, highly localized mitochondrial Ca2+ hotspots. Our results indicate that mitochondria decode the spike firing frequency and the Hebbian temporal coincidences into the Ca2+ signals, which are further translated into the metabolic output and most probably lead to long-term changes in synaptic efficacy.

High-frequency oscillations and sequence generation in two-population models of hippocampal region CA1.

Hippocampal sharp wave/ripple oscillations are a prominent pattern of collective activity, which consists of a strong overall increase of activity with superimposed (140 − 200 Hz) ripple oscillations. Despite its prominence and its experimentally demonstrated importance for memory consolidation, the mechanisms underlying its generation are to date not understood. Several models assume that recurrent networks of inhibitory cells alone can explain the generation and main characteristics of the ripple oscillations. Recent experiments, however, indicate that in addition to inhibitory basket cells, the pattern requires in vivo the activity of the local population of excitatory pyramidal cells. Here, we study a model for networks in the hippocampal region CA1 incorporating such a local excitatory population of pyramidal neurons. We start by investigating its ability to generate ripple oscillations using extensive simulations. Using biologically plausible parameters, we find that short pulses of external excitation triggering excitatory cell spiking are required for sharp/wave ripple generation with oscillation patterns similar to in vivo observations. Our model has plausible values for single neuron, synapse and connectivity parameters, random connectivity and no strong feedforward drive to the inhibitory population. Specifically, whereas temporally broad excitation can lead to high-frequency oscillations in the ripple range, sparse pyramidal cell activity is only obtained with pulse-like external CA3 excitation. Further simulations indicate that such short pulses could originate from dendritic spikes in the apical or basal dendrites of CA1 pyramidal cells, which are triggered by coincident spike arrivals from hippocampal region CA3. Finally we show that replay of sequences by pyramidal neurons and ripple oscillations can arise intrinsically in CA1 due to structured connectivity that gives rise to alternating excitatory pulse and inhibitory gap coding; the latter denotes phases of silence in specific basket cell groups, which induce selective disinhibition of groups of pyramidal neurons. This general mechanism for sequence generation leads to sparse pyramidal cell and dense basket cell spiking, does not rely on synfire chain-like feedforward excitation and may be relevant for other brain regions as well.

Blue Light-Induced Retinal Neuronal Injury and Amelioration by Commercially Available Blue Light-Blocking Lenses.

Blue light exposure-induced retinal damage has been extensively studied. Although many in vitro studies have shown the benefits of blue light-blocking lenses (BBL) there have been few comprehensive in vivo studies to assess the effects of BBL. We investigated the influence of blue light exposure using light-emitting diodes on retinal histology and visual cortex neurons in rodents. We also considered whether retinal and cortical changes induced by blue light could be ameliorated with blue light-blocking lenses. A total of n = 24 (n = 6 in each group; control, light exposure without lenses, two different BBLs)) male Wistar rats were subjected to blue light exposure (LEDs, 450–500 lux) without or with BBLs (400–490 nm) for 28 days on a 12:12 h light–dark cycle. Histological analysis of retinae revealed apoptosis and necrosis of the retinal pigment epithelium (RPE), photoreceptors, and inner retina in the light exposure (LE) group, along with increase caspase-3 immunostaining in the ganglion cell layer (p < 0.001). BBL groups showed less caspase-3 immunostaining compared with the LE group (p < 0.001). V1-L5PNs (primary visual cortex layer 5 pyramidal neurons) demonstrated reduced branching and intersections points for apical (p < 0.001) and basal (p < 0.05) dendrites following blue light exposure. Blue light-blocking lenses significantly improved the number of basal branching points compared with the LE group. Our study shows that prolonged exposure to high levels of blue light pose a significant hazard to the visual system resulting in damage to the retina with the associated remodeling of visual cortex neurons. BBL may offer moderate protection against exposure to high levels of blue light.

Notes on Visual Cortical Feedback and Feedforward Connections.

The largely dissociated laminar distribution patterns of feedforward (FFD) and feedback (FBK) cortical connnections in sensory areas of nonhuman primates (NHP) have figured prominently in ideas of network organization and cortical hierarchy. While convenient, this emphasis does not take full account of the actual anatomical complexity. There is a diversity of FFD and FBK neuronal subtypes (cf. the corticogeniculate (CG) projections, where the fact of multiple CG neuronal subtypes inspired ideas of parallel processing). There is a complex architecture of recurrent connections, where FFD and FBK connections interact together and with numerous other cortical and subcortical connections, in ways still to be elucidated. Importantly, the laminar patterns so apparent at the global level, are less so from the perspective of postsynaptic dendritic input maps. Both supragranular FFD and FBK projecting neurons have apical dendrites in layer 1, and both FFD and FBK neurons can directly access inputs to layer 4 (respectively, via basal dendrites of neurons in deep layer 3 and apical denrites of infragranular neurons). Here, I briefly discuss some of the basic anatomical questions regarding FFD- FBK processing, still unanswered at the cellular level, and propose that the corrrelation with a functional hierarchy is less evident than often suggested.

Effects of electroacupuncture on BNDF/mTORC1 signaling pathway and synaptic plasticity in prefrontal cortex of rats exposed to chronic unpredictable mild stress

To investigate the effects of electroacupuncture (EA) on the expression of related proteins in the brain-derived neurotrophic factor (BDNF)/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and synapse-associated proteins and the density of dendrite spines in the prefrontal cortex (PFC) of depression model rats, and to reveal the underlying mechanism by which EA regulates the synaptic plasticity to improve depressive symptoms. Thirty-six healthy male Sprague-Dawley (SD) rats were randomly divided into normal group, model group, EA group, and scopolamine (SCOP) group, with 9 in each group. The depression model was established by exposing rats to chronic unpredictable mild stress (CUMS) combined with isolated feeding. Rats in the EA group were treated with EA (2 Hz/100 Hz, 1-1.2 mA) at "Baihui" (GV20), "Yintang" (EX-HN3), "Hegu" (LI4), and "Taichong" (LR3), 20 min each time, once per day, for 14 d, while those in the SCOP group treated with intraperitoneal injection of 25 μg/kg SCOP, once every 16 h, for 14 d. The sucrose preference and feeding latency of rats in each group were observed in the sucrose preference test (SPT) and novelty-suppressed feeding test. The expression levels of proteins in the BDNF/mTORC1 signaling pathway and synapse-associated proteins PSD95, Synapsin Ⅰ, and GluR1 were assayed by Western blot. Golgi-Cox staining was conducted for exploring the total density of dendritic spines on the apical dendrites of layer Ⅴ pyramidal neurons in PFC as well as the densities of mature, immature, and filopodial-like dendritic spines. Compared with the normal group, the model group exhibited significantly decreased sucrose preference (P<0.001), prolonged feeding latency (P<0.001), down-regulated BDNF, mTORC1, phosphorylated mTORC1 (p-mTORC1), PSD95, Synapsin Ⅰ, and GluR1 expression (P<0.001，P<0.01), and diminished total, mature, and immature spine dendritic densities (P<0.001). Compared with the model group, both EA and SCOP remarkably increased the sucrose preference (P<0.001), shortened the feeding latency (P<0.001), up-regulated the BDNF, mTORC1, p-mTORC1, PSD95, Synapsin Ⅰ, and GluR1 expression in PFC(P<0.05，P<0.01，P<0.001), and elevated the total and immature spine dendritic densities (P<0.001,P<0.01). The density of filopodial-like dendritic spine in the EA group was obviously enhanced (P<0.01), whereas the mature dendritic spine density in the SCOP group rose sharply (P<0.001). However, there were no significant differences between the EA group and SCOP group (P>0.05). EA alleviates the depressive symptoms of CUMS model rats possibly by up-regulating the expression of proteins in the BDNF/mTORC1 signaling pathway and synapse-asso-ciated proteins PSD95, Synapsin Ⅰ, and GluR1, increasing the dendritic spine density, and enhancing the synaptic plasticity in PFC.

Chronic altered light–dark cycle differentially affects hippocampal CA1 and DG neuronal arborization in diurnal and nocturnal rodents

ABSTRACT The hippocampus, an extension of the temporal part of the cerebral cortex, plays a crucial role in learning and memory. Structural and functional complexity within the hippocampus is greatly affected by a variety of external environmental stimuli including alteration in the light–dark (LD) cycle. The effect of altered LD cycle in learning and memory associated cognitive impairment has been reported in rodents. However, a comparative study of underlying neuronal changes between nocturnal and diurnal species is not well explored. The objective of the present study was to explore the morphological changes in hippocampal CA1 and DG neurons in response to prolonged constant condition viz. constant light (LL) and constant darkness (DD) in diurnal squirrels and nocturnal mice. Animals (n = 5/group) were placed in chronocubicle under 12:12 h LD, LL and DD. After four weeks, brain tissues were collected and processed for Golgi-Cox staining to analyze morphological changes in CA1 and DG neurons. The total and basal dendritic length, basal dendrite number, branch end, the diameter of apical dendrite and spine density were analyzed. The results showed a significant reduction in structural complexity of CA1 and DG neurons of squirrels exposed to prolonged constant darkness, whereas mice showed a significant increase as compared to LD. However, a significantly reduced neuronal complexity was observed in both squirrels and mice exposed to prolonged constant light. The results obtained were further confirmed by Sholl analysis of CA1 and DG neurons. The present study suggests that prolonged constant light may cause adverse effects on the neuronal complexity of both diurnal and nocturnal animals, but constant darkness may cause adverse effects mainly to the diurnal animals.

Sensory deprivation leads to subpopulation-specific changes in layer 6 corticothalamic cells.

The effect of sensory deprivation on anatomical and physiological properties in two genetically defined types of layer 6 corticothalamic pyramidal cells in mouse somatosensory barrel cortex was investigated using in vitro electrophysiology. The two types analysed were the L6-Ntsr1 subtype, found preferentially in the upper region of layer 6 and projecting to both ventral posterior medial nucleus of the thalamus and posterior medial nucleus of the thalamus, and the L6-Drd1a subtype, located mostly in the lower regions of layer 6 and projecting to posterior medial nucleus. We found that the apical dendrite in L6-Ntsr1 cells is longer and more branched, compared with L6-Drd1a cells, and that the increase in firing frequency with increasing current stimulation is steeper in L6-Drd1a cells. Sensory deprivation was achieved clipping one row of whiskers from birth until the day of experiment (16 ± 2days). Mice of this age are actively exploring. In L6-Ntsr1, but not in L6-Drd1a cells, sensory deprivation decreased apical and basal dendrite outgrowth, and calcium influx evoked by backpropagating action potentials. These results contribute to the ongoing functional characterisation of corticothalamic layer 6 cells and indicate differences in the postnatal cortical refinement of two distinct corticothalamic circuits.

Two-Argument Activation Functions Learn Soft XOR Operations Like Cortical Neurons.

Neurons in the brain are complex machines with distinct functional compartments that interact nonlinearly. In contrast, neurons in artificial neural networks abstract away this complexity, typically down to a scalar activation function of a weighted sum of inputs. Here we emulate more biologically realistic neurons by learning canonical activation functions with two input arguments, analogous to basal and apical dendrites. We use a network-in-network architecture where each neuron is modeled as a multilayer perceptron with two inputs and a single output. This inner perceptron is shared by all units in the outer network. Remarkably, the resultant nonlinearities often produce soft XOR functions, consistent with recent experimental observations about interactions between inputs in human cortical neurons. When hyperparameters are optimized, networks with these nonlinearities learn faster and perform better than conventional ReLU nonlinearities with matched parameter counts, and they are more robust to natural and adversarial perturbations.