Apical Dendrites Of Pyramidal Cells Research Articles

Frequency-dependent membrane polarization across neocortical cell types and subcellular elements by transcranial alternating current stimulation.

Objective.Transcranial alternating current stimulation (tACS) is a non-invasive brain stimulation technique that directly interacts with ongoing brain oscillations in a frequency-dependent manner. However, it remains largely unclear how the cellular effects of tACS vary between cell types and subcellular elements.Approach.In this study, we use a set of morphologically realistic models of neocortical neurons to simulate the cellular response to uniform oscillating electric fields (EFs). We systematically characterize the membrane polarization in the soma, axons, and dendrites with varying field directions, intensities, and frequencies.Main results.Pyramidal cells are more sensitive to axial EF that is roughly parallel to the cortical column, while interneurons are sensitive to axial EF and transverse EF that is tangent to the cortical surface. Membrane polarization in each subcellular element increases linearly with EF intensity, and its slope, i.e. polarization length, highly depends on the stimulation frequency. At each frequency, pyramidal cells are more polarized than interneurons. Axons usually experience the highest polarization, followed by the dendrites and soma. Moreover, a visible frequency resonance presents in the apical dendrites of pyramidal cells, while the other subcellular elements primarily exhibit low-pass filtering properties. In contrast, each subcellular element of interneurons exhibits complex frequency-dependent polarization. Polarization phase in each subcellular element of cortical neurons lags that of field and exhibits high-pass filtering properties. These results demonstrate that the membrane polarization is not only frequency-dependent, but also cell type- and subcellular element-specific. Through relating effective length and ion mechanism with polarization, we emphasize the crucial role of cell morphology and biophysics in determining the frequency-dependent membrane polarization.Significance.Our findings highlight the diverse polarization patterns across cell types as well as subcellular elements, which provide some insights into the tACS cellular effects and should be considered when understanding the neural spiking activity by tACS.

Responses of pyramidal cell somata and apical dendrites in mouse visual cortex over multiple days

The apical dendrites of pyramidal neurons in sensory cortex receive primarily top-down signals from associative and motor regions, while cell bodies and nearby dendrites are heavily targeted by locally recurrent or bottom-up inputs from the sensory periphery. Based on these differences, a number of theories in computational neuroscience postulate a unique role for apical dendrites in learning. However, due to technical challenges in data collection, little data is available for comparing the responses of apical dendrites to cell bodies over multiple days. Here we present a dataset collected through the Allen Institute Mindscope’s OpenScope program that addresses this need. This dataset comprises high-quality two-photon calcium imaging from the apical dendrites and the cell bodies of visual cortical pyramidal neurons, acquired over multiple days in awake, behaving mice that were presented with visual stimuli. Many of the cell bodies and dendrite segments were tracked over days, enabling analyses of how their responses change over time. This dataset allows neuroscientists to explore the differences between apical and somatic processing and plasticity.

Basic Principles of Electroencephalogram

Electroencephalogram(EEG)signals are mainly generated by postsynaptic potentials(EPSP)in the apical dendrites of pyramidal cells in the cortex. The mechanism of generation of interictal epileptiform discharges(IED)is paroxysmal depolarization shift(PDS). IEDs are negative towards the cortical surface and positive towards the white matter. To interpret EEG, readers should know normal EEG waveforms of wakefulness and sleep, normal variants such as wicket spikes or small sharp spikes, and artifacts such as eye movements or electromyography. Overinterpretation of EEG is a major cause of misdiagnosis; therefore, the accurate identification of IED is essential. The International Federation of Clinical Neurophysiology has proposed a criteria for the identification of IED. Long-term video-EEG is useful for correct diagnosis and localization of the epileptogenic zone in the setting of presurgical evaluation of intractable epilepsy and is also useful for the differential diagnosis of epileptic seizures and non-epileptic events. Clinical history and symptomatology are of utmost importance for correct diagnosis. Diagnosis should not be made using only EEG findings.

Mastication stimuli enhance the learning ability of weaning-stage rats, altering the hippocampal neuron transcriptome and micromorphology.

Mastication stimuli are known to relieve senile dementia in human and animal studies. However, few studies have focused on its effect on weaning-stage animals and the underlying molecular processes. In this study, 3-week-old male rats were raised on a powdered (P-group) or chow (C-group) diet for 8 days, and their behavior was examined using the Y-maze and novel object recognition tests. In the Y-maze test, the C-group rats showed a larger alternation ratio than the P-group rats. In the novel object recognition test, the C-group rats exhibited a significantly larger discrimination index for novel objects than for familiar objects, but the P-group rats did not. We then compared the hippocampal neuron morphology and transcriptome between the groups. C-group rats exhibited larger dendrite branch numbers in the apical dendrites of pyramidal cells in the cornu ammonis 1 (CA1) region and a larger spine density in the basal dendrites of CA1 neurons than the P-group rats. Using DNA microarray analysis, we identified 621 (P < C) and 96 (P > C) genes that were differentially expressed between the groups. These genes were enriched in functional terms related to dendrite growth and included the Igf2, RhoA, and Rho GEF genes, most of which were upregulated in the C-group. These results suggest that the mastication stimuli during the weaning period can enhance the learning ability of rats by increasing the dendrite branches of hippocampal CA1 neurons and by regulating genes related to dendrite growth.

Postnatal Cytoarchitecture and Neurochemical Hippocampal Dysfunction in Down Syndrome.

Although the prenatal hippocampus displays deficits in cellular proliferation/migration and volume, which are later associated with memory deficits, little is known about the effects of trisomy 21 on postnatal hippocampal cellular development in Down syndrome (DS). We examined postnatal hippocampal neuronal profiles from autopsies of DS and neurotypical (NTD) neonates born at 38-weeks’-gestation up to children 3 years of age using antibodies against non-phosphorylated (SMI-32) and phosphorylated (SMI-34) neurofilament, calbindin D-28k (Calb), calretinin (Calr), parvalbumin (Parv), doublecortin (DCX) and Ki-67, as well as amyloid precursor protein (APP), amyloid beta (Aβ) and phosphorylated tau (p-tau). Although the distribution of SMI-32-immunoreactive (-ir) hippocampal neurons was similar at all ages in both groups, pyramidal cell apical and basal dendrites were intensely stained in NTD cases. A greater reduction in the number of DCX-ir cells was observed in the hippocampal granule cell layer in DS. Although the distribution of Calb-ir neurons was similar between the youngest and oldest NTD and DS cases, Parv-ir was not detected. Conversely, Calr-ir cells and fibers were observed at all ages in DS, while NTD cases displayed mainly Calr-ir fibers. Hippocampal APP/Aβ-ir diffuse-like plaques were seen in DS and NTD. By contrast, no Aβ1–42 or p-tau profiles were observed. These findings suggest that deficits in hippocampal neurogenesis and pyramidal cell maturation and increased Calr immunoreactivity during early postnatal life contribute to cognitive impairment in DS.

Macrophage Migration Inhibitory Factor Alters Functional Properties of CA1 Hippocampal Neurons in Mouse Brain Slices.

Neuroinflammation is implicated in a host of neurological insults, such as traumatic brain injury (TBI), ischemic stroke, Alzheimer’s disease, Parkinson’s disease, and epilepsy. The immune response to central nervous system (CNS) injury involves sequelae including the release of numerous cytokines and chemokines. Macrophage migration inhibitory factor (MIF), is one such cytokine that is elevated following CNS injury, and is associated with the prognosis of TBI, and ischemic stroke. MIF has been identified in astrocytes and neurons, and some of the trophic actions of MIF have been related to its direct and indirect actions on astrocytes. However, the potential modulation of CNS neuronal function by MIF has not yet been explored. This study tests the hypothesis that MIF can directly influence hippocampal neuronal function. MIF was microinjected into the hippocampus and the genetically encoded calcium indicator, GCaMP6f, was used to measure Ca2+ events in acute adult mouse brain hippocampal slices. Results demonstrated that a single injection of 200 ng MIF into the hippocampus significantly increased baseline calcium signals in CA1 pyramidal neuron somata, and altered calcium responses to N-methyl-d-aspartate (NMDA) + D-serine in pyramidal cell apical dendrites located in the stratum radiatum. These data are the first to show direct effects of MIF on hippocampal neurons and on NMDA receptor function. Considering that MIF is elevated after brain insults such as TBI, the data suggest that, in addition to the previously described role of MIF in astrocyte reactivity, elevated MIF can have significant effects on neuronal function in the hippocampus.

Differences in Sodium Channel Densities in the Apical Dendrites of Pyramidal Cells of the Electrosensory Lateral Line Lobe.

Heterogeneity of neural properties within a given neural class is ubiquitous in the nervous system and permits different sub-classes of neurons to specialize for specific purposes. This principle has been thoroughly investigated in the hindbrain of the weakly electric fish A. leptorhynchus in the primary electrosensory area, the Electrosensory Lateral Line lobe (ELL). The pyramidal cells (PCs) that receive inputs from tuberous electroreceptors are organized in three maps in distinct segments of the ELL. The properties of these cells vary greatly across maps due to differences in connectivity, receptor expression, and ion channel composition. These cells are a seminal example of bursting neurons and their bursting dynamic relies on the presence of voltage-gated Na+ channels in the extensive apical dendrites of the superficial PCs. Other ion channels can affect burst generation and their expression varies across ELL neurons and segments. For example, SK channels cause hyperpolarizing after-potentials decreasing the likelihood of bursting, yet bursting propensity is similar across segments. We question whether the depolarizing mechanism that generates the bursts presents quantitative differences across segments that could counterbalance other differences having the opposite effect. Although their presence and role are established, the distribution and density of the apical dendrites’ Na+ channels have not been quantified and compared across ELL maps. Therefore, we test the hypothesis that Na+ channel density varies across segment by quantifying their distribution in the apical dendrites of immunolabeled ELL sections. We found the Na+ channels to be two-fold denser in the lateral segment (LS) than in the centro-medial segment (CMS), the centro-lateral segment (CLS) being intermediate. Our results imply that this differential expression of voltage-gated Na+ channels could counterbalance or interact with other aspects of neuronal physiology that vary across segments (e.g., SK channels). We argue that burst coding of sensory signals, and the way the network regulates bursting, should be influenced by these variations in Na+ channel density.

Amplifying the redistribution of somato-dendritic inhibition by the interplay of three interneuron types.

GABAergic interneurons play an important role in shaping the activity of excitatory pyramidal cells (PCs). How the various inhibitory cell types contribute to neuronal information processing, however, is not resolved. Here, we propose a functional role for a widespread network motif consisting of parvalbumin- (PV), somatostatin- (SOM) and vasoactive intestinal peptide (VIP)-expressing interneurons. Following the idea that PV and SOM interneurons control the distribution of somatic and dendritic inhibition onto PCs, we suggest that mutual inhibition between VIP and SOM cells translates weak inputs to VIP interneurons into large changes of somato-dendritic inhibition of PCs. Using a computational model, we show that the neuronal and synaptic properties of the circuit support this hypothesis. Moreover, we demonstrate that the SOM-VIP motif allows transient inputs to persistently switch the circuit between two processing modes, in which top-down inputs onto apical dendrites of PCs are either integrated or cancelled.

Complementary networks of cortical somatostatin interneurons enforce layer specific control.

The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input.

Convergent synaptic inputs to layer 1 cells of mouse cortex

We used whole cell recordings from slice preparations of mouse cortex to identify various inputs to neurons of layer 1. Two sensory cortical areas were targeted: a primary somatosensory area, namely, the barrel cortex of S1, and a higher order visual area, namely, V2M. Results were similar from both areas. By activating local inputs using photostimulation with caged glutamate, we also identified glutamatergic (and possibly GABAergic) inputs from all lower layers plus GABAergic inputs from nearby layer 1 neurons. However, the patterns of such inputs to layer 1 neurons showed great variation among cells. In separate experiments, we found that electrical stimulation of axons running parallel to the cortical surface in layer 1 also evoked a variety of convergent input types to layer 1 neurons, including glutamatergic "drivers" and "modulators" plus classic modulatory inputs, including serotonergic, nicotinic, α- and β-adrenergic, from subcortical sites. Given that these layer 1 cells significantly affect the responses of other cortical neurons, especially via affecting the apical dendrites of pyramidal cells so important to cortical functioning, their role in cortical processing is significant. We believe that the data presented here lead to better understanding of the functioning of layer 1 neurons in their role of influencing cortical processing.

Diversity of dendritic morphology and entorhinal cortex synaptic effectiveness in mouse CA2 pyramidal neurons.

Excitatory synaptic inputs from specific brain regions are often targeted to distinct dendritic arbors on hippocampal pyramidal neurons. Recent work has suggested that CA2 pyramidal neurons respond robustly and preferentially to excitatory input into the stratum lacunosum moleculare (SLM), with a relatively modest response to Schaffer collateral excitatory input into stratum radiatum (SR) in acute mouse hippocampal slices, but the extent to which this difference may be explained by morphology is unknown. In an effort to replicate these findings and to better understand the role of dendritic morphology in shaping responses from proximal and distal synaptic sites, we measured excitatory postsynaptic currents and action potentials in CA2 pyramidal cells in response to SR and SLM stimulation and subsequently analyzed confocal images of the filled cells. We found that, in contrast to previous reports, SR stimulation evoked substantial responses in all recorded CA2 pyramidal cells. Strikingly, however, we found that not all neurons responded to SLM stimulation, and in those neurons that did, responses evoked by SLM and SR were comparable in size and effectiveness in inducing action potentials. In a comprehensive morphometric analysis of CA2 pyramidal cell apical dendrites, we found that the neurons that were unresponsive to SLM stimulation were the same ones that lacked substantial apical dendritic arborization in the SLM. Neurons responsive to both SR and SLM stimulation had roughly equal amounts of dendritic branching in each layer. Remarkably, our study in mouse CA2 generally replicates the work characterizing the diversity of CA2 pyramidal cells in the guinea pig hippocampus. We conclude, then, that like in guinea pig, mouse CA2 pyramidal cells have a diverse apical dendrite morphology that is likely to be reflective of both the amount and source of excitatory input into CA2 from the entorhinal cortex and CA3.

Reelin Signaling Inactivates Cofilin to Stabilize the Cytoskeleton of Migrating Cortical Neurons.

Neurons are highly polarized cells. They give rise to several dendrites but only one axon. In addition, many neurons show a preferred orientation. For example, pyramidal neurons of the cerebral cortex extend their apical dendrites toward the cortical surface while their axons run in opposite direction toward the white matter. This characteristic orientation reflects the migratory trajectory of a pyramidal cell during cortical development: the leading process (the future apical dendrite) extends toward the marginal zone (MZ) and the trailing process (the future axon) toward the intermediate zone (IZ) while the cells migrate radially to reach their destination in the cortical plate (CP). In this review article, we summarize the function of Reelin, an extracellular matrix protein synthesized by Cajal-Retzius cells in the MZ, in the development of the characteristic orientation of the leading processes running perpendicular to the cortical surface. Reelin promotes migration toward the cortical surface since late-generated cortical neurons in the reeler mutant are unable to reach upper cortical layers. Likewise, Reelin is important for the orientation and maintenance of the leading processes of migrating neurons since they are misoriented in the developing reeler cortex, as are the apical dendrites of pyramidal cells in the mature mutant. Reelin-induced phosphorylation of cofilin, an actin-associated protein, is crucial since pyramidal neurons transfected by in utero electroporation (IUE) with a non-phosphorylatable form of cofilin (cofilinS3A) show severe migration defects reminiscent of those in the reeler mutant. Remarkably, migration of neurons in the cortex of reeler mice was partially rescued by transfecting them with LIM kinase 1 (LIMK1), the kinase that induces phosphorylation of cofilin at serine3, or with a pseudo-phosphorylated cofilin mutant (cofilinS3E). Together these results indicate that Reelin-induced phosphorylation of cofilin is an important component in the orientation and directed migration of cortical neurons and in their correct lamination.

Stress and Loss of Adult Neurogenesis Differentially Reduce Hippocampal Volume

BackgroundHippocampal volume loss is a hallmark of clinical depression. Chronic stress produces volume loss in the hippocampus in humans and atrophy of CA3 pyramidal cells and suppression of adult neurogenesis in rodents. MethodsTo investigate the relationship between decreased adult neurogenesis and stress-induced changes in hippocampal structure and volume, we compared the effects of chronic unpredictable restraint stress and inhibition of neurogenesis in a rat pharmacogenetic model. ResultsChronic unpredictable restraint stress over 4 weeks decreased total hippocampal volume, reflecting loss of volume in all hippocampal subfields and in both dorsal and ventral hippocampus. In contrast, complete inhibition of adult neurogenesis for 4 weeks led to volume reduction only in the dentate gyrus. With prolonged inhibition of neurogenesis for 8 or 16 weeks, volume loss spread to the CA3 region, but not CA1. Combining stress and inhibition of adult neurogenesis did not have additive effects on the magnitude of volume loss but did produce a volume reduction throughout the hippocampus. One month of chronic unpredictable restraint stress and inhibition of adult neurogenesis led to atrophy of pyramidal cell apical dendrites in dorsal CA3 and to neuronal reorganization in ventral CA3. Stress also significantly affected granule cell dendrites. ConclusionsThe findings suggest that adult neurogenesis is required to maintain hippocampal volume but is not responsible for stress-induced volume loss.

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat.

The nucleus reuniens (RE) and entorhinal cortex (EC) provide monosynaptic excitatory inputs to the apical dendrites of pyramidal cells and to interneurons with dendrites in stratum lacunosum moleculare (LM) of hippocampal field CA1. However, whether the RE and EC inputs interact at the cellular level is unknown. In this electrophysiological in vivo study, low-frequency stimulation was used to selectively activate each projection at its origin; field excitatory postsynaptic potentials (fEPSPs) were recorded in CA1. We applied (1) paired pulses to RE or EC, (2) combined paired pulses to RE and EC, and (3) simultaneously paired pulses to RE/EC. The main findings are that: (a) stimulation of either RE- or EC-evoked subthreshold fEPSPs, displaying paired pulse facilitation (PPF), (b) subthreshold fEPSPs evoked by combined stimulation did not display heterosynaptic PPF, and (c) simultaneous stimulation of RE/EC resulted in enhanced subthreshold fEPSPs in proximal LM displaying a nonlinear interaction. CSD analyses of RE/EC-evoked depth profiles revealed a nonlinear enlargement of the 'LM sink-radiatum source' configuration and the appearance of an additional small sink-source pair close to stratum pyramidale, likely reflecting (peri)somatic inhibition. The nonlinear interaction between both inputs indicates that RE and EC axons form synapses, at least partly, onto the same dendritic compartments of CA1 pyramidal cells. We propose that low-frequency activation of the RE-CA1 input facilitates the entorhinal-hippocampal dialogue, and may synchronize the neocortical-hippocampal slow oscillation which is relevant for hippocampal-dependent memory consolidation.

Effects of a GABAC Receptor Blocker on the Formation of Evoked Potentials in Neuronal Columns in the Rat Somatosensory Cortex

Microelectrode studies of the evoked activity of neuronal columns in the barrel cortex in rats showed that the GABAC receptor blocker 1,2,5,6-tetrahydropyridin-4-ylmethylphosphonic acid (TPMPA) had an activatory effect on the secondary components of evoked potentials (EP) mainly of the upper afferent modules of columns as compared with the lower efferent layers. This is evidence that GABAC receptors are located on the presynaptic terminals of thalamocortical glutamatergic afferents and ascending apical dendrites of pyramidal cells. Blockade of GABAC influences with TPMPA led to dose-dependent depolarization of afferents with development of presynaptic inhibition and suppression of the primary responses (PR) of EP. The different effects of the GABAC receptor blocker on the secondary components of EP in the upper layers of the cortex are due to the development of afterhyperpolarization of neurons after high-amplitude PR and afterdepolarization after low-amplitude responses, with subsequent activation of different voltage-gated channels and the formation of different gradients in the direct current (DC) potential of the cortex.

Exposure to a diet high in fat attenuates dendritic spine density in the medial prefrontal cortex.

A key factor in the development of obesity is the overconsumption of food calorically high in fat. Overconsumption of food high in fat not only promotes weight gain but elicits changes in reward processing. No studies to date have examined whether consumption of a high-fat (HF) diet alters structural plasticity in brain areas critical for reward processing, which may account for persistent changes in behavior and psychological function by reorganizing synaptic connectivity. To test whether dietary fat may induce structural plasticity we placed rats on one of three dietary conditions: ad libitum standard chow (SC), ad libitum 60% HF (HF-AL), or calorically matched 60% HF (HF-CM) for 3weeks and then quantified dendritic spine density and type on basal and apical dendrites of pyramidal cells in layer V of the medial prefrontal cortex (mPFC) and medium spiny neurons (MSNs) of the nucleus accumbens. Our results demonstrate a significant reduction in the density of thin spines on the apical and basal segments of dendrites within the infralimbic, but not prelimbic, mPFC.

Hippocampal Transcriptome Profile of Persistent Memory Rescue in a Mouse Model of THRA1 Mutation-Mediated Resistance to Thyroid Hormone.

Hypothyroidism due to THRA1 (gene coding for thyroid hormone receptor α1) mutation-mediated Resistance to Thyroid Hormone (RTH) has been recently reported in human and is associated with memory deficits similar to those found in a mouse model for Thra1 mutation mediated RTH (Thra1+/m mice). Here, we show that a short-term treatment of Thra1+/m mice with GABAA receptor antagonist pentylenetetrazol (PTZ) completely and durably rescues their memory performance. In the CA1 region of the hippocampus, improvement of memory is associated with increased in long-term potentiation (LTP) and an augmentation of density of dendritic spines (DDS) onto the apical dendrites of pyramidal cells reflecting an increase in the local excitatory drive. Unbiased gene profiling analysis of hippocampi of treated Thra1+/+ and Thra1+/m mice were performed two weeks and three months post treatment and identified co-expression modules that include differentially expressed genes related with and predicting higher memory, LTP and DDS in the hippocampi of PTZ-treated animals. We observed that PTZ treatment changed similar sets of genes in both Thra1+/+ and Thra1+/m mice, which are known to be involved in memory consolidation and neurotransmission dynamics and could participate in the persistent effects of PTZ on memory recovery.

Investigation of the Cerebral Cortex Using Magnetoencephalography(MEG)

Cortical neurons are excited by signals from the thalamus that are conducted via thalamocortical fibers. As the cortex receives these signals, electric currents are conducted through the apical dendrites of pyramidal cells in the cerebral cortex. These electric currents generate magnetic fields. These electric and magnetic currents can be recorded by electroencephalography (EEG) and magnetoencephalography (MEG), respectively. The spatial resolution of MEG is higher than that of EEG because magnetic fields, unlike electric fields, are not affected by current conductivity. MEG also has several advantages over functional magnetic resonance imaging (fMRI). It (1) is completely non-invasive; (2) measures neuronal activity rather than blood flow or metabolic changes; (3) has a higher temporal resolution than fMRI on the order of milliseconds; (4) enables the measurement of stimulus-evoked and event-related responses; (5) enables the analysis of frequency (i.e., brain rhythm) response, which means that physiological changes can be analyzed spatiotemporally; and (6) enables the detailed analysis of results from an individual subject, which eliminates the need to average results over several subjects. This latter advantage of MEG therefore enables the analysis of inter-individual differences.

Synaptic proteins in the hippocampus indicative of increased neuronal activity in CA3 in schizophrenia.

In schizophrenia, hippocampal perfusion is increased and declarative memory function is degraded. Based on an a priori model of hippocampal dysfunction in schizophrenic psychosis, the authors postulated molecular and cellular changes in CA3 consistent with increased NMDA receptor signaling. Postmortem hippocampal subfield tissue (CA3, CA1) from subjects with schizophrenia and nonpsychiatric comparison subjects was analyzed using Western blotting and Golgi histochemistry to examine the hypothesized outcomes. The GluN2B-containing NMDA receptors (GluN2B/GluN1) and their associated postsynaptic membrane protein PSD95 were both increased in schizophrenia in CA3 tissue, but not in CA1 tissue. Quantitative analyses of Golgi-stained hippocampal neurons showed an increase in spine density on CA3 pyramidal cell apical dendrites (stratum radiatum) and an increase in the number of thorny excrescences. The hippocampal data are consistent with increased excitatory signaling in CA3 and/or with an elevation in silent synapses in CA3, a state that may contribute to an increase in long-term potentiation in CA3 with subsequent stimulation and "unsilencing." These changes are plausibly associated with increased associational activity in CA3, with degraded declarative memory function, and with formation of false memories with psychotic content. The influence of these hyperactive hippocampal projections on targets in the limbic neocortex could contribute to components of schizophrenia manifestations in other cerebral regions.

Hippocampal Subfields and Major Depressive Disorder

Hippocampal Subfields and Major Depressive Disorder