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Current Biology : CB Sep 2023Hippocampal sharp-wave ripples (SPW-Rs) are critical for memory consolidation and retrieval. The neuronal content of spiking during SPW-Rs is believed to be under the...
Hippocampal sharp-wave ripples (SPW-Rs) are critical for memory consolidation and retrieval. The neuronal content of spiking during SPW-Rs is believed to be under the influence of neocortical inputs via the entorhinal cortex (EC). Optogenetic silencing of the medial EC (mEC) reduced the incidence of SPW-Rs with minor impacts on their magnitude or duration, similar to local CA1 silencing. The effect of mEC silencing on CA1 firing and field potentials was comparable to the effect of transient cortex-wide DOWN states of non-REM (NREM) sleep, implying that decreased SPW-R incidence in both cases is due to tonic disfacilitation of hippocampal circuits. The neuronal composition of CA1 pyramidal neurons during SPW-Rs was altered by mEC silencing but was restored immediately after silencing. We suggest that the mEC provides both tonic and transient influences on hippocampal network states by timing the occurrence of SPW-Rs and altering their neuronal content.
Topics: Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells; Memory Consolidation; Action Potentials
PubMed: 37572665
DOI: 10.1016/j.cub.2023.07.039 -
Journal of Neuroscience Research Sep 2023This review discusses neuroanatomical aspects of the three main monoaminergic systems innervating the basolateral nuclear complex (BNC) of the amygdala (serotonergic,... (Review)
Review
This review discusses neuroanatomical aspects of the three main monoaminergic systems innervating the basolateral nuclear complex (BNC) of the amygdala (serotonergic, noradrenergic, and dopaminergic systems). It mainly focuses on immunohistochemical (IHC) and in situ hybridization (ISH) studies that have analyzed the relationship of specific monoaminergic inputs and their receptors to specific neuronal subtypes in the BNC in order to better understand the anatomical substrates of the monoaminergic modulation of BNC circuitry. First, light and electron microscopic IHC investigations identifying the main BNC neuronal subpopulations and characterizing their local circuitry, including connections with discrete PN compartments and other INs, are reviewed. Then, the relationships of each of the three monoaminergic systems to distinct PN and IN cell types, are examined in detail. For each system, the neuronal targets and their receptor expression are discussed. In addition, pertinent electrophysiological investigations are discussed. The last section of the review compares and contrasts various aspects of each of the three monoaminergic systems. It is concluded that the large number of different receptors, each with a distinct mode of action, expressed by distinct cell types with different connections and functions, should offer innumerable ways to subtlety regulate the activity of the BNC by therapeutic drugs in psychiatric diseases in which there are alterations of BNC monoaminergic modulatory systems, such as in anxiety disorders, depression, and drug addiction. It is suggested that an important area for future studies is to investigate how the three systems interact in concert at the neuronal and neuronal network levels.
Topics: Basolateral Nuclear Complex; Neuroanatomy; Neurons; Amygdala; Microscopy, Electron
PubMed: 37166098
DOI: 10.1002/jnr.25201 -
The Journal of Neuroscience : the... Oct 2023A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is...
A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and CA2 pyramidal neurons (PNs). A role for CA2 in seizure generation was suggested based on findings of a reduction in CA2 synaptic inhibition (Williamson and Spencer, 1994) and the presence of interictal-like spike activity in CA2 in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-induced status epilepticus (PILO-SE) mouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study, we explored the cellular basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches in PILO-SE male and female mice. We report a widespread decrease in the density of pro-cholecystokinin-immunopositive (CCK) interneurons and a functional impairment of CCK interneuron-mediated inhibition of CA2 PNs. We also found a disruption in the perisomatic perineuronal net in the CA2 stratum pyramidale. Such pathologic alterations may contribute to an enhanced excitation of CA2 PNs and CA2-dependent seizure activity in the PILO-SE mouse model. Impaired synaptic inhibition in hippocampal circuits has been identified as a key feature that contributes to the emergence and propagation of seizure activity in human patients and animal models of temporal lobe epilepsy (TLE). Among the hippocampal subfields, the CA2 region is particularly resilient to seizure-associated neurodegeneration and has been suggested to play a key role in seizure activity in TLE. Here we report that perisomatic inhibition of CA2 pyramidal neurons mediated by cholecystokinin-expressing interneurons is selectively reduced in acute hippocampal slices from epileptic mice. Parvalbumin-expressing interneurons, in contrast, appear relatively conserved in epileptic mice. These findings advance our understanding of the cellular mechanisms underlying inhibitory disruption in hippocampal circuits in a mouse model of spontaneous recurring seizures.
Topics: Humans; Male; Female; Mice; Animals; CA2 Region, Hippocampal; Epilepsy, Temporal Lobe; Cholecystokinin; Hippocampus; Interneurons; Seizures; Pilocarpine; Status Epilepticus; Disease Models, Animal
PubMed: 37643861
DOI: 10.1523/JNEUROSCI.2091-22.2023 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2023Postnatal regulation of dendritic spine formation and refinement in cortical pyramidal neurons is critical for excitatory/inhibitory balance in neocortical networks....
Postnatal regulation of dendritic spine formation and refinement in cortical pyramidal neurons is critical for excitatory/inhibitory balance in neocortical networks. Recent studies have identified a selective spine pruning mechanism in the mouse prefrontal cortex mediated by class 3 Semaphorins and the L1 cell adhesion molecules, neuron-glia related cell adhesion molecule, Close Homolog of L1, and L1. L1 cell adhesion molecules bind Ankyrin B, an actin-spectrin adaptor encoded by Ankyrin2, a high-confidence gene for autism spectrum disorder. In a new inducible mouse model (Nex1Cre-ERT2: Ank2flox: RCE), Ankyrin2 deletion in early postnatal pyramidal neurons increased spine density on apical dendrites in prefrontal cortex layer 2/3 of homozygous and heterozygous Ankyrin2-deficient mice. In contrast, Ankyrin2 deletion in adulthood had no effect on spine density. Sema3F-induced spine pruning was impaired in cortical neuron cultures from Ankyrin B-null mice and was rescued by re-expression of the 220 kDa Ankyrin B isoform but not 440 kDa Ankyrin B. Ankyrin B bound to neuron-glia related CAM at a cytoplasmic domain motif (FIGQY1231), and mutation to FIGQH inhibited binding, impairing Sema3F-induced spine pruning in neuronal cultures. Identification of a novel function for Ankyrin B in dendritic spine regulation provides insight into cortical circuit development, as well as potential molecular deficiencies in autism spectrum disorder.
Topics: Mice; Animals; Dendritic Spines; Ankyrins; Autism Spectrum Disorder; Pyramidal Cells; Prefrontal Cortex; Mice, Knockout
PubMed: 37642601
DOI: 10.1093/cercor/bhad311 -
Cellular and Molecular Life Sciences :... Nov 2023Mutations of large conductance Ca- and voltage-activated K channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific...
Mutations of large conductance Ca- and voltage-activated K channels (BK) are associated with cognitive impairment. Here we report that CA1 pyramidal neuron-specific conditional BK knock-out (cKO) mice display normal locomotor and anxiety behavior. They do, however, exhibit impaired memory acquisition and retrieval in the Morris Water Maze (MWM) when compared to littermate controls (CTRL). In line with cognitive impairment in vivo, electrical and chemical long-term potentiation (LTP) in cKO brain slices were impaired in vitro. We further used a genetically encoded fluorescent K biosensor and a Ca-sensitive probe to observe cultured hippocampal neurons during chemical LTP (cLTP) induction. cLTP massively reduced intracellular K concentration ([K]) while elevating L-Type Ca channel- and NMDA receptor-dependent Ca oscillation frequencies. Both, [K] decrease and Ca oscillation frequency increase were absent after pharmacological BK inhibition or in cells lacking BK. Our data suggest that L-Type- and NMDAR-dependent BK-mediated K outflow significantly contributes to hippocampal LTP, as well as learning and memory.
Topics: Mice; Animals; Long-Term Potentiation; Large-Conductance Calcium-Activated Potassium Channels; Neuronal Plasticity; Hippocampus; Neurons; Mice, Knockout
PubMed: 37989805
DOI: 10.1007/s00018-023-05016-y -
Science Advances Feb 2024Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly...
Understanding the plasticity of neuronal networks is an emerging field of (patho-) physiological research, yet the underlying cellular mechanisms remain poorly understood. Gamma oscillations (30 to 80 hertz), a biomarker of cognitive performance, require and potentiate glutamatergic transmission onto parvalbumin-positive interneurons (PVIs), suggesting an interface for cell-to-network plasticity. In ex vivo local field potential recordings, we demonstrate long-term potentiation of hippocampal gamma power. Gamma potentiation obeys established rules of PVI plasticity, requiring calcium-permeable AMPA receptors (CP-AMPARs) and metabotropic glutamate receptors (mGluRs). A microcircuit computational model of CA3 gamma oscillations predicts CP-AMPAR plasticity onto PVIs critically outperforms pyramidal cell plasticity in increasing gamma power and completely accounts for gamma potentiation. We reaffirm this ex vivo in three PVI-targeting animal models, demonstrating that gamma potentiation requires PVI-specific signaling via a Gq/PKC pathway comprising mGluR5 and a Gi-sensitive, PKA-dependent pathway. Gamma activity-dependent, metabotropically mediated CP-AMPAR plasticity on PVIs may serve as a guiding principle in understanding network plasticity in health and disease.
Topics: Animals; Parvalbumins; Hippocampus; Long-Term Potentiation; Signal Transduction; Interneurons; Neuronal Plasticity
PubMed: 38295164
DOI: 10.1126/sciadv.adj7427 -
Journal of Psychiatric Research Nov 2023Bipolar disorder has been associated with a decrease in hippocampal size, and lithium appears to reverse this neuroanatomical abnormality. The objective of this work was...
Bipolar disorder has been associated with a decrease in hippocampal size, and lithium appears to reverse this neuroanatomical abnormality. The objective of this work was to evaluate, at a cellular level, the size of both cell body and nucleus of pyramidal neurons located throughout the Cornu Ammonis (CA1 to CA4 regions). To perform this duty, we used 16 rats that were randomized into two groups: control and dietary lithium-treated. After one month, they were sacrificed and their brains removed for histopathological analysis. Serial photos of the entire Cornu Ammonis were taken and, after dividing them into 4 regions of interest, we measured the cell body and nucleus on each pyramidal neuron belonging to the first 5 photos of each region of interest. As a result of this histological analysis, cell body area and nuclear area were significantly larger in the experimental group in a specific area of the Cornu Ammonis that could correspond to CA2 or the transition between CA1 and CA2. These results suggest that the effect of lithium is not homogeneous throughout the hippocampus and allows directing future studies to a specific area of this structure.
Topics: Animals; Pyramidal Cells; Rats; Male; Disease Models, Animal; Hippocampus; Rats, Wistar; Antimanic Agents; CA1 Region, Hippocampal
PubMed: 37826875
DOI: 10.1016/j.jpsychires.2023.10.001 -
Philosophical Transactions of the Royal... Jul 2024Neurons are plastic. That is, they change their activity according to different behavioural conditions. This endows pyramidal neurons with an incredible computational... (Review)
Review
Neurons are plastic. That is, they change their activity according to different behavioural conditions. This endows pyramidal neurons with an incredible computational power for the integration and processing of synaptic inputs. Plasticity can be investigated at different levels of investigation within a single neuron, from spines to dendrites, to synaptic input. Although most of our knowledge stems from the brain slice preparation, plasticity plays a vital role during behaviour by providing a flexible substrate for the execution of appropriate actions in our ever-changing environment. Owing to advances in recording techniques, the plasticity of neurons and the neural networks in which they are embedded is now beginning to be realized in the intact brain. This review focuses on the structural and functional synaptic plasticity of pyramidal neurons with a specific focus on the latest developments from studies. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Topics: Pyramidal Cells; Neuronal Plasticity; Animals; Brain; Long-Term Potentiation; Synapses; Humans
PubMed: 38853566
DOI: 10.1098/rstb.2023.0231 -
Nature Communications Nov 2023Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride...
Cortical activity patterns are strongly modulated by fast synaptic inhibition mediated through ionotropic, chloride-conducting receptors. Consequently, chloride homeostasis is ideally placed to regulate activity. We therefore investigated the stability of baseline [Cl] in adult mouse neocortex, using in vivo two-photon imaging. We found a two-fold increase in baseline [Cl] in layer 2/3 pyramidal neurons, from day to night, with marked effects upon both physiological cortical processing and seizure susceptibility. Importantly, the night-time activity can be converted to the day-time pattern by local inhibition of NKCC1, while inhibition of KCC2 converts day-time [Cl] towards night-time levels. Changes in the surface expression and phosphorylation of the cation-chloride cotransporters, NKCC1 and KCC2, matched these pharmacological effects. When we extended the dark period by 4 h, mice remained active, but [Cl] was modulated as for animals in normal light cycles. Our data thus demonstrate a daily [Cl] modulation with complex effects on cortical excitability.
Topics: Animals; Mice; Chlorides; Symporters; Pyramidal Cells; Homeostasis; Visual Cortex
PubMed: 37925453
DOI: 10.1038/s41467-023-42711-7 -
Science (New York, N.Y.) Apr 2024The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly...
The computational capabilities of neuronal networks are fundamentally constrained by their specific connectivity. Previous studies of cortical connectivity have mostly been carried out in rodents; whether the principles established therein also apply to the evolutionarily expanded human cortex is unclear. We studied network properties within the human temporal cortex using samples obtained from brain surgery. We analyzed multineuron patch-clamp recordings in layer 2-3 pyramidal neurons and identified substantial differences compared with rodents. Reciprocity showed random distribution, synaptic strength was independent from connection probability, and connectivity of the supragranular temporal cortex followed a directed and mostly acyclic graph topology. Application of these principles in neuronal models increased dimensionality of network dynamics, suggesting a critical role for cortical computation.
Topics: Animals; Humans; Nerve Net; Pyramidal Cells; Rodentia; Synapses; Temporal Lobe; Patch-Clamp Techniques
PubMed: 38635709
DOI: 10.1126/science.adg8828