Heksor: the central nervous system substrate of an adaptive behaviour

The Journal of Physiology, Journal Year: 2022, Volume and Issue: 600(15), P. 3423 - 3452

Published: June 30, 2022

Abstract Over the past half‐century, largely hardwired central nervous system (CNS) of 1970 has become ubiquitously plastic CNS today, in which change is rule not exception. This transformation complicates a question neuroscience: how are adaptive behaviours – that serve needs individual acquired and maintained through life? It poses more basic question: do many share CNS? compels neuroscience to adopt new paradigm. The core this paradigm entity with unique properties, here given name heksor from Greek hexis . A distributed network neurons synapses changes itself as needed maintain key features an behaviour, make behaviour satisfactory. Through their concurrent changes, numerous heksors negotiate properties they all use. Heksors keep state negotiated equilibrium enables each its behaviour. based on create supported by animal human studies interactions among old behaviours, explains otherwise inexplicable results, underlies promising approaches restoring impaired injury or disease. Furthermore, offers potentially important answers extant questions, such generation function spontaneous neuronal activity, aetiology muscle synergies, control homeostatic plasticity. image

Language: Английский

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Dendritic axon origin enables information gating by perisomatic inhibition in pyramidal neurons

Science, Journal Year: 2022, Volume and Issue: 377(6613), P. 1448 - 1452

Published: Sept. 22, 2022

Information processing in neuronal networks involves the recruitment of selected neurons into coordinated spatiotemporal activity patterns. This sparse activation results from widespread synaptic inhibition conjunction with neuron-specific excitation. We report selective hippocampal pyramidal cells patterned network activity. During ripple oscillations awake mice, spiking is much more likely which axon originates a basal dendrite rather than soma. High-resolution recordings vitro and computer modeling indicate that these spikes are elicited by input to axon-carrying thus escape perisomatic inhibition. Pyramidal somatic origin can be activated during blocking their The active ensembles determined axonal morphological features.

Language: Английский

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Sodium channel endocytosis drives axon initial segment plasticity

Science Advances, Journal Year: 2023, Volume and Issue: 9(37)

Published: Sept. 15, 2023

Activity-dependent plasticity of the axon initial segment (AIS) endows neurons with ability to adapt action potential output changes in network activity. Action initiation at AIS highly depends on clustering voltage-gated sodium channels, but molecular mechanisms regulating their remain largely unknown. Here, we developed genetic tools label endogenous channels and scaffolding protein, reveal nanoscale organization longitudinally image hippocampal slices primary cultures. We find that N -methyl- d -aspartate receptor activation causes both long-term synaptic depression rapid internalization within minutes. The clathrin-mediated endocytosis distal increases threshold for generation. These data a fundamental mechanism activity-dependent reorganization suggests intrinsic excitability shares conserved features plasticity.

Language: Английский

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LRRC37B is a human modifier of voltage-gated sodium channels and axon excitability in cortical neurons

Cell, Journal Year: 2023, Volume and Issue: 186(26), P. 5766 - 5783.e25

Published: Dec. 1, 2023

The enhanced cognitive abilities characterizing the human species result from specialized features of neurons and circuits. Here, we report that hominid-specific gene LRRC37B encodes a receptor expressed in cortical pyramidal (CPNs) selectively localized to axon initial segment (AIS), subcellular compartment triggering action potentials. Ectopic expression mouse CPNs vivo leads reduced intrinsic excitability, distinctive feature some classes CPNs. Molecularly, binds secreted ligand FGF13A voltage-gated sodium channel (Nav) β-subunit SCN1B. concentrates inhibitory effects on Nav function, thereby reducing specifically at AIS level. Electrophysiological recordings adult slices reveal lower neuronal excitability expressing LRRC37B. thus acts as species-specific modifier neuron linking genome cell evolution, with important implications for brain function diseases.

Language: Английский

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Brief Sensory Deprivation Triggers Cell Type-Specific Structural and Functional Plasticity in Olfactory Bulb Neurons

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(10), P. 2135 - 2151

Published: Jan. 22, 2021

Can alterations in experience trigger different plastic modifications neuronal structure and function, if so, how do they integrate at the cellular level? To address this question, we interrogated circuitry mouse olfactory bulb responsible for earliest steps odor processing. We induced experience-dependent plasticity mice of either sex by blocking one nostril day, a minimally invasive manipulation that leaves sensory organ undamaged is akin to natural transient blockage suffered during common mild rhinal infections. found such brief deprivation produced structural functional highly specialized bulbar cell type: axon-bearing dopaminergic neurons glomerular layer. After 24 h naris occlusion, axon initial segment (AIS) became significantly shorter, modification was also associated with decrease intrinsic excitability. These effects were specific AIS-positive subpopulation because no excitability observed AIS-negative cells. Moreover, occlusion changes AIS excitatory neurons, mitral/tufted external tufted cells, nor did it alter their By targeting subpopulation, early networks might act fine-tune processing face continually fluctuating inputs. SIGNIFICANCE STATEMENT Sensory need be so can adapt incoming stimuli. see cells circuits change response challenges, blocked just naturally relevant occurs cold. induces forms axonal subtype: interneurons. In contrast, properties axon-lacking neighboring remained unchanged. Within same circuits, types therefore make distinct an ever-changing landscape.

Language: Английский

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Adaptive control of synaptic plasticity integrates micro- and macroscopic network function

Neuropsychopharmacology, Journal Year: 2022, Volume and Issue: 48(1), P. 121 - 144

Published: Aug. 29, 2022

Synaptic plasticity configures interactions between neurons and is therefore likely to be a primary driver of behavioral learning development. How this microscopic-macroscopic interaction occurs poorly understood, as researchers frequently examine models within particular ranges abstraction scale. Computational neuroscience machine offer theoretically powerful analyses in neural networks, but results are often siloed only coarsely linked biology. In review, we connections these areas, asking how network computations change function diverse features vice versa. We review can controlled at synapses by calcium dynamics neuromodulatory signals, the manifestation changes their impacts specialized circuits. conclude that metaplasticity-defined broadly adaptive control plasticity-forges across scales governing what groups can't learn about, when, ends. The metaplasticity discuss acts co-opting Hebbian mechanisms, shifting properties, routing activity brain systems. Asking operations go awry should also useful for understanding pathology, which address context autism, schizophrenia Parkinson's disease.

Language: Английский

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Early Life Stress Induces Different Behaviors in Adolescence and Adulthood May Related With Abnormal Medial Prefrontal Cortex Excitation/Inhibition Balance

Frontiers in Neuroscience, Journal Year: 2022, Volume and Issue: 15

Published: Jan. 4, 2022

Early life stress is thought to be a risk factor for emotional disorders, particularly depression and anxiety. Although the excitation/inhibition (E/I) imbalance has been implicated in neuropsychiatric whether early affects E/I balance medial prefrontal cortex at various developmental stages unclear. In this study, rats exposed maternal separation (MS) that exhibited well-established paradigm were used evaluate adolescence (postnatal day P43-60) adulthood (P82-100) by behavior tests, whole-cell recordings, microdialysis coupled with high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis. First, behavioral tests revealed MS induced both anxiety- depressive-like behaviors adolescent but only adult rats. Second, increased action potential frequency of synaptic transmission onto L5 pyramidal neurons prelimbic (PrL) brain region while decreasing Finally, increases extracellular glutamate levels decreased paired-pulse ratio evoked excitatory postsynaptic currents (EPSCs) PrL contrast, EPSCs The present results reveal key role different MS-induced disorders may related altered probability presynaptic release stages.

Language: Английский

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Neuron-oligodendrocyte potassium shuttling at nodes of Ranvier protects against inflammatory demyelination

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(7)

Published: Jan. 31, 2023

Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS. Increasing evidence suggests that vulnerable neurons in MS exhibit fatal metabolic exhaustion over time, phenomenon hypothesized to be caused by chronic hyperexcitability. Axonal Kv7 (outward-rectifying) and oligodendroglial Kir4.1 (inward-rectifying) potassium channels have important roles regulating neuronal excitability at around nodes Ranvier. Here, we studied spatial functional relationship between assessed transcriptional signatures cortical retinal projection under physiological conditions. We found both became dysregulated experimental autoimmune encephalomyelitis (EAE), with being chronically downregulated channel subunits transiently upregulated during demyelination. Further, observed pharmacological opening retigabine reduced hyperexcitability human EAE neurons, improved clinical signs, rescued pathology oligodendrocyte-Kir4.1-deficient (OL-Kir4.1-deficient) mice. In summary, our findings indicate neuron-OL compensatory interactions promoted resilience through identify activation nodal as neuroprotective strategy against

Language: Английский

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Aberrant axon initial segment plasticity and intrinsic excitability of ALS hiPSC motor neurons

Cell Reports, Journal Year: 2023, Volume and Issue: 42(12), P. 113509 - 113509

Published: Nov. 29, 2023

Dysregulated neuronal excitability is a hallmark of amyotrophic lateral sclerosis (ALS). We sought to investigate how functional changes the axon initial segment (AIS), site action potential generation, could impact in ALS human induced pluripotent stem cell (hiPSC) motor neurons. find that early TDP-43 and C9orf72 hiPSC neurons show an increase length AIS impaired activity-dependent plasticity linked abnormal homeostatic regulation activity intrinsic hyperexcitability. In turn, these hyperactive drive increased spontaneous myofiber contractions vitro units. contrast, late postmortem shortening, progress hypoexcitability. At molecular level, aberrant expression master scaffolding protein ankyrin-G AIS-specific voltage-gated sodium channels mirror dynamic function excitability. Our results point toward as important dysfunction

Language: Английский

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Neocortical pyramidal neurons with axons emerging from dendrites are frequent in non-primates, but rare in monkey and human

eLife, Journal Year: 2022, Volume and Issue: 11

Published: April 20, 2022

The canonical view of neuronal function is that inputs are received by dendrites and somata, become integrated in the somatodendritic compartment upon reaching a sufficient threshold, generate axonal output with axons emerging from cell body. latter not necessarily case. Instead, may originate dendrites. terms ‘axon carrying dendrite’ (AcD) ‘AcD neurons’ have been coined to describe this feature. In rodent hippocampus, AcD cells shown be functionally ‘privileged’, since here can circumvent somatic integration lead immediate action potential initiation axon. Here, we report on diversity axon origins neocortical pyramidal rodent, ungulate, carnivore, primate. Detection methods were Thy-1-EGFP labeling mouse, retrograde biocytin tracing rat, cat, ferret, macaque, SMI-32/βIV-spectrin immunofluorescence pig, Golgi staining macaque human. We found non-primate mammals, 10–21% layers II–VI had an AcD. marked contrast, human, proportion was lower particularly low for supragranular neurons. A comparison six cortical areas (being sensory, association, limbic nature) three macaques yielded percentages which varied factor 2 between individuals. Unexpectedly, white matter postnatal cat aged human cortex exhibit AcDs much higher percentages. addition, interneurons assessed developing adult at type-specific proportions some types than cells. Our findings expand current knowledge regarding distribution neocortex taxa, strikingly differ primates where these mainly deeper matter.

Language: Английский

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