scholarly journals Inhibitory control of synaptic signals preceding motor action in mouse frontal cortex

2021 ◽  
Author(s):  
Chunlei Zhang ◽  
Fani Koukouli ◽  
Manuela Allegra ◽  
Cantin Ortiz ◽  
Hsin-Lun Kao ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Frontal Cortex ◽  
Motor Planning ◽  
Inhibitory Neurons ◽  
Excitatory Synapses ◽  
Motor Action ◽  
Whole Cell Patch Clamp ◽  
Preparatory Activity

Preparatory activity in the frontal cortex preceding movement onset is thought to represent a neuronal signature of motor planning. However, how excitatory and inhibitory synaptic inputs to frontal neurons are integrated during movement preparation remains unclear. Here we address this question by performing in vivo whole-cell patch-clamp recordings in the secondary motor cortex (MOs) of head-fixed mice moving on a treadmill. We find that both superficial and deep principal neurons show slowly increasing (~10 s) membrane potential and spike rate ramps preceding the onset of spontaneous, self-paced running periods. By contrast, in animals trained to perform a goal-directed task, both membrane potential and spike ramps are characterized by larger amplitudes and accelerated kinetics during preparation of goal-driven movement. To determine the role of local inhibitory neurons in shaping these task-dependent preparatory signals, we chemogenetically suppressed the activity of specific interneuron subpopulations in untrained animals. Inactivation of parvalbumin-positive (PV+) interneurons leads to depolarized membrane potential ramps with increased amplitudes during preparation of movement, while inactivation of somatostatin-positive (SOM+) interneurons abolishes membrane potential ramps. A computational model of the local MOs circuit shows that SOM+-mediated inhibition of PV+ interneurons in conjunction with recurrent connectivity among the principal neurons can reproduce slow ramping signals, while plasticity of excitatory synapses on SOM+ interneurons can explain the acceleration of these signals in trained animals. Together, our data reveal that local inhibitory neurons play distinct roles in controlling task-dependent preparatory ramping signals when MOs neurons integrate external inputs during motor planning.

scholarly journals Seizures start as silent microseizures by neuronal ensembles

2018 ◽  
Author(s):  
Michael Wenzel ◽  
Jordan P. Hamm ◽  
Darcy S. Peterka ◽  
Rafael MD Yuste
Keyword(s):  
Calcium Imaging ◽  
Travelling Wave ◽  
Inhibitory Neurons ◽  
Neural Activation ◽  
Calcium Dynamics ◽  
Neuronal Ensembles ◽  
Two Photon ◽  
Step Model

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.

scholarly journals 0074 Inhibitory Neurons in the Dorsomedial Medulla Promote REM Sleep

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A30-A30
Author(s):  
J Stucynski ◽  
A Schott ◽  
J Baik ◽  
J Hong ◽  
F Weber ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Nrem Sleep ◽  
Inhibitory Neurons ◽  
Brain State ◽  
Sleep Regulation ◽  
Optogenetic Stimulation ◽  
Electrophysiological Recordings ◽  
Stimulation Of

Abstract Introduction The neural circuits controlling rapid eye movement (REM) sleep, and in particular the role of the medulla in regulating this brain state, remains an active area of study. Previous electrophysiological recordings in the dorsomedial medulla (DM) and electrical stimulation experiments suggested an important role of this area in the control of REM sleep. However the identity of the involved neurons and their precise role in REM sleep regulation are still unclear. Methods The properties of DM GAD2 neurons in mice were investigated through stereotaxic injection of CRE-dependent viruses in conjunction with implantation of electrodes for electroencephalogram (EEG) and electromyogram (EMG) recordings and optic fibers. Experiments included in vivo calcium imaging (fiber photometry) across sleep and wake states, optogenetic stimulation of cell bodies, chemogenetic excitation and suppression (DREADDs), and connectivity mapping using viral tracing and optogenetics. Results Imaging the calcium activity of DM GAD2 neurons in vivo indicates that these neurons are most active during REM sleep. Optogenetic stimulation of DM GAD2 neurons reliably triggered transitions into REM sleep from NREM sleep. Consistent with this, chemogenetic activation of DM GAD2 neurons increased the amount of REM sleep while inhibition suppressed its occurrence and enhanced NREM sleep. Anatomical tracing revealed that DM GAD2 neurons project to several areas involved in sleep / wake regulation including the wake-promoting locus coeruleus (LC) and the REM sleep-suppressing ventrolateral periaquaductal gray (vlPAG). Optogenetic activation of axonal projections from DM to LC, and DM to vlPAG was sufficient to induce REM sleep. Conclusion These experiments demonstrate that DM inhibitory neurons expressing GAD2 powerfully promote initiation of REM sleep in mice. These findings further characterize the dorsomedial medulla as a critical structure involved in REM sleep regulation and inform future investigations of the REM sleep circuitry. Support R01 HL149133

Role of EDHF in conduction of vasodilation along hamster cheek pouch arterioles in vivo

2000 ◽  
Vol 278 (6) ◽  
pp. H1832-H1839 ◽  
Author(s):  
Donald G. Welsh ◽  
Steven S. Segal
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Smooth Muscle Cells ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Cytochrome P 450 ◽  
Arteriolar Diameter

We tested whether local and conducted responses to ACh depend on factors released from endothelial cells (EC) in cheek pouch arterioles of anesthetized hamsters. ACh was delivered from a micropipette (1 s, 500 nA), while arteriolar diameter (rest, ∼40 μm) was monitored at the site of application (local) and at 520 and 1,040 μm upstream (conducted). Under control conditions, ACh elicited local (22–65 μm) and conducted (14–44 μm) vasodilation. Indomethacin (10 μM) had no effect, whereas N ω-nitro-l-arginine (100 μM) reduced local and conducted vasodilation by 5–8% ( P < 0.05). Miconazole (10 μM) or 17-octadecynoic acid (17-ODYA; 10 μM) diminished local vasodilation by 15–20% and conducted responses by 50–70% ( P < 0.05), suggesting a role for cytochrome P-450 (CYP) metabolites in arteriolar responses to ACh. Membrane potential ( E m) was recorded in smooth muscle cells (SMC) and in EC identified with dye labeling. At rest (control E m, typically −30 mV), ACh evoked local (15–32 mV) and conducted (6–31 mV) hyperpolarizations in SMC and EC. Miconazole inhibited SMC and EC hyperpolarization, whereas 17-ODYA inhibited hyperpolarization of SMC but not of EC. Findings indicate that ACh-induced release of CYP metabolites from arteriolar EC evoke SMC hyperpolarization that contributes substantively to conducted vasodilation.

scholarly journals Wnt-Frizzled Signaling Regulates Activity-Mediated Synapse Formation

2021 ◽  
Vol 14 ◽  
Author(s):  
Samuel Teo ◽  
Patricia C. Salinas
Keyword(s):  
Wnt Signaling ◽  
Neuronal Activity ◽  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Model Systems ◽  
Mammalian Brain ◽  
Excitatory Synapses ◽  
Wnt Ligands

The formation of synapses is a tightly regulated process that requires the coordinated assembly of the presynaptic and postsynaptic sides. Defects in synaptogenesis during development or in the adult can lead to neurodevelopmental disorders, neurological disorders, and neurodegenerative diseases. In order to develop therapeutic approaches for these neurological conditions, we must first understand the molecular mechanisms that regulate synapse formation. The Wnt family of secreted glycoproteins are key regulators of synapse formation in different model systems from invertebrates to mammals. In this review, we will discuss the role of Wnt signaling in the formation of excitatory synapses in the mammalian brain by focusing on Wnt7a and Wnt5a, two Wnt ligands that play an in vivo role in this process. We will also discuss how changes in neuronal activity modulate the expression and/or release of Wnts, resulting in changes in the localization of surface levels of Frizzled, key Wnt receptors, at the synapse. Thus, changes in neuronal activity influence the magnitude of Wnt signaling, which in turn contributes to activity-mediated synapse formation.

scholarly journals Deficiency of intellectual disability-related gene Brpf1 reduced inhibitory neurotransmission and Map2k7 expression in GABAergic interneurons

2021 ◽  
Author(s):  
Jingli Cao ◽  
Weiwei Xian ◽  
Maierdan Palihati ◽  
Yu Zhu ◽  
Guoxiang Wang ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Dendritic Morphology ◽  
Gabaergic Interneurons ◽  
Related Gene ◽  
Inhibitory Neurotransmission ◽  
Whole Cell Patch Clamp ◽  
Developmental Niche ◽  
And Function

AbstractIntellectual disability is closely related to impaired GABA neurotransmission. Brpf1 was specifically expressed in medial ganglionic eminence (MGE), a developmental niche of GABAergic interneurons, and patients with BRPF1 mutations were mentally retarded. To test its role in development and function of MGE-derived GABAergic interneurons, we performed immunofluorescence staining, whole-cell patch-clamp, MGE transplantation and mRNA-Seq to understand its effect on neuronal differentiation, dendritic morphology, electrophysiology, migration and gene regulation, using mouse MGE-derived GABAergic interneurons infected with AAV-shBrpf1. We found a decreasing trend on parvalbumin+ interneuron differentiation. Moreover, increased firing threshold, decreased number of evoked APs, and a reduced amplitude of mIPSCs were observed before any significant change of MAP2+ dendritic morphology and in vivo migration appeared. Finally, mRNA-Seq analysis revealed that genes related to neurodevelopment and synaptic transmission such as Map2k7 were dysregulated. Our results demonstrated a key role of Brpf1 in inhibitory neurotransmission and related gene expression of GABAergic interneurons.

scholarly journals Stress-induced antinociception to noxious heat requires α1A-adrenaline receptors of spinal inhibitory neurons in mice

2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Sawako Uchiyama ◽  
Kohei Yoshihara ◽  
Riku Kawanabe ◽  
Izuho Hatada ◽  
Keisuke Koga ◽  
...  
Keyword(s):  
Antinociceptive Effect ◽  
Conditional Knockout ◽  
Acute Exposure ◽  
Substantia Gelatinosa ◽  
Inhibitory Neurons ◽  
Noxious Heat ◽  
Similar Reduction ◽  
Whole Cell Patch Clamp ◽  
The Central Nervous System

AbstractIt is well known that acute exposure to physical stress produces a transient antinociceptive effect (called stress-induced analgesia [SIA]). One proposed mechanism for SIA involves noradrenaline (NA) in the central nervous system. NA has been reported to activate inhibitory neurons in the spinal dorsal horn (SDH), but its in vivo role in SIA remains unknown. In this study, we found that an antinociceptive effect on noxious heat after acute exposure to restraint stress was impaired in mice with a conditional knockout of α1A-adrenaline receptors (α1A-ARs) in inhibitory neurons (Vgat-Cre;Adra1aflox/flox mice). A similar reduction was also observed in mice treated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine, a selective neurotoxin for NAergic neurons in the locus coeruleus (LC). Furthermore, whole-cell patch-clamp recordings using spinal cord slices revealed that NA-induced increase in the frequency of spontaneous inhibitory postsynaptic currents in the substantia gelatinosa neurons was suppressed by silodosin, an α1A-AR antagonist, and by conditional knockout of α1A-ARs in inhibitory neurons. Moreover, under unstressed conditions, the antinociceptive effects of intrathecal NA and phenylephrine on noxious heat were lost in Vgat-Cre;Adra1aflox/flox mice. Our findings suggest that activation of α1A-ARs in SDH inhibitory neurons, presumably via LC-NAergic neurons, is necessary for SIA to noxious heat.

scholarly journals D-Chiro-Inositol Improves Sperm Mitochondrial Membrane Potential: In Vitro Evidence

2020 ◽  
Vol 9 (5) ◽  
pp. 1373 ◽  
Author(s):  
Rosita A. Condorelli ◽  
Federica Barbagallo ◽  
Aldo E. Calogero ◽  
Rossella Cannarella ◽  
Andrea Crafa ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Sperm Motility ◽  
Mitochondrial Membrane ◽  
Polycystic Ovarian Syndrome ◽  
Biologically Active ◽  
Ovarian Syndrome

The use of inositols in endocrinological clinical practice is increasingly widespread. Most of the existing evidence concerns myoinositol (MYO), the most abundant form in nature, especially in women with polycystic ovarian syndrome. We have previously shown that MYO increases sperm motility in patients with asthenozoospermia by the increase of sperm mitochondrial membrane potential (MMP), a biofunctional sperm parameter closely associated to sperm motility. The aim of this study was to evaluate the effects of D-chiro-inositol (DCI), another biologically active isoform of inositols, on sperm MMP, as data on this matter has never been released so far. To accomplish this, semen samples from 15 patients with asthenozoospermia and 15 healthy normozoospermic men were incubated with increasing concentrations of DCI (0, 75, and 750 µg/mL) or phosphate buffer saline for 30 min. Incubation with DCI significantly improved sperm MMP at lower concentrations, and with shorter incubation length than those used in our similar MYO studies. In conclusion, these findings indicate that DCI positively impacts on sperm mitochondrial function in vitro. Studies aimed at assessing the role of DCI in the treatment of asthenozoospermia in-vivo are warranted.

scholarly journals Distinct in vivo dynamics of excitatory synapses onto cortical pyramidal neurons and inhibitory interneurons

2021 ◽  
Author(s):  
Joshua B. Melander ◽  
Aran Nayebi ◽  
Bart C. Jongbloets ◽  
Dale A. Fortin ◽  
Maozhen Qin ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Synaptic Weight ◽  
Barrel Cortex ◽  
Inhibitory Neurons ◽  
Inhibitory Interneurons ◽  
Excitatory Synapses ◽  
Cell Type ◽  
Cortical Function ◽  
Cell Type Specific

SUMMARYCortical function relies on the balanced activation of excitatory and inhibitory neurons. However, little is known about the organization and dynamics of shaft excitatory synapses onto cortical inhibitory interneurons, which cannot be easily identified morphologically. Here, we fluorescently visualize the excitatory postsynaptic marker PSD-95 at endogenous levels as a proxy for excitatory synapses onto layer 2/3 pyramidal neurons and parvalbumin-positive (PV+) inhibitory interneurons in the mouse barrel cortex. Longitudinal in vivo imaging reveals that, while synaptic weights in both neuronal types are log-normally distributed, synapses onto PV+ neurons are less heterogeneous and more stable. Markov-model analyses suggest that the synaptic weight distribution is set intrinsically by ongoing cell type-specific dynamics, and substantial changes are due to accumulated gradual changes. Synaptic weight dynamics are multiplicative, i.e., changes scale with weights, though PV+ synapses also exhibit an additive component. These results reveal that cell type-specific processes govern cortical synaptic strengths and dynamics.

scholarly journals Presynaptic PTPσ organizes neurotransmitter release machinery at excitatory synapses

2020 ◽  
Author(s):  
Kyung Ah Han ◽  
Hee-Yoon Lee ◽  
Dongseok Lim ◽  
Jungsu Shin ◽  
Taek Han Yoon ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Conditional Knockout ◽  
Excitatory Synapses ◽  
Conditional Deletion ◽  
Evolutionarily Conserved ◽  
Bona Fide ◽  
Receptor Tyrosine Phosphatases ◽  
Postsynaptic Target

AbstractLeukocyte common antigen-related receptor tyrosine phosphatases (LAR-RPTPs) are evolutionarily conserved presynaptic organizers. The synaptic role of vertebrate LAR-RPTPs in vivo, however, remains unclear. This study systematically analyzed the effects of genetic deletions of LAR-RPTP genes by generating single conditional knockout (cKO) mice targeting PTPσ and PTPδ. Although the numbers of synapses were reduced in cultured neurons deficient in individual PTPs, abnormalities in synaptic transmission, synaptic ultrastructures, and vesicle localization were observed only in PTPσ-deficient neurons. Strikingly, loss of presynaptic PTPσ reduced neurotransmitter release prominently at excitatory synapses, concomitant with drastic reductions in excitatory innervations onto postsynaptic target areas in vivo. However, postsynaptic PTPσ deletion had no effect on excitatory synaptic strength. Furthermore, conditional deletion of PTPσ in ventral CA1 specifically altered anxiety-like behaviors. Taken together, these results demonstrate that PTPσ is a bona fide presynaptic adhesion molecule that controls neurotransmitter release and excitatory inputs.

scholarly journals Regulation of Hippocampal Excitatory Synapses by the Zdhhc5 Palmitoyl Acyl Transferase

2020 ◽  
Author(s):  
Jordan J. Shimell ◽  
Andrea Globa ◽  
Marja D. Sepers ◽  
Angela R. Wild ◽  
Nusrat Matin ◽  
...  
Keyword(s):  
Inhibitory Synapses ◽  
Excitatory Synapses ◽  
Silent Synapses ◽  
Synapse Plasticity ◽  
Hippocampal Synapses ◽  
The Brain ◽  
Spine Number

ABSTRACTPalmitoylation is the most common post-translational lipid modification in the brain; however, the role of palmitoylation and palmitoylating enzymes in the nervous system remains elusive. One of these enzymes, Zdhhc5, has previously been shown to regulate synapse plasticity. Here, we report that Zdhhc5 is also essential for the formation of excitatory, but not inhibitory synapses both in vitro and in vivo. We demonstrate in vitro that this is dependent on Zdhhc5’s enzymatic activity, its localization at the plasma membrane, and its C-terminal domain which has been shown to be truncated in a patient with schizophrenia. Loss of Zdhhc5 in mice results in a decrease in the density of excitatory hippocampal synapses accompanied by alterations in membrane capacitance and synaptic currents, consistent with an overall decrease in spine number and silent synapses. These findings reveal an important role for Zdhhc5 in the formation and/or maintenance of excitatory synapses.

Sign in / Sign up

Export Citation Format

Share Document