Adipokines set neural tone by regulating synapse number

Mapping Intimacies ◽

10.1101/781526 ◽

2019 ◽

Author(s):

Ava E. Brent ◽

Akhila Rajan

Keyword(s):

State Energy ◽

Inhibitory Neurons ◽

Neuron Activity ◽

List Type ◽

Neuronal Function ◽

Synaptic Contacts ◽

Nutrient Surplus ◽

Energy Store ◽

Energy Sensing ◽

Negative Tone

SummaryEnergy sensing neural circuits decide to expend or conserve resources by integrating tonic steady-state energy store information with phasic signals for hunger and food intake. Tonic signals, in the form of adipose tissue-derived adipokines, set the baseline level of energy-sensing neuron activity, providing context for interpretation of phasic messages. However, the mechanism by which tonic adipokine information establishes baseline neuronal function is unclear. Here we show that Upd2, a Drosophila Leptin ortholog, regulates actin-based synapse reorganization by reducing inhibitory synaptic contacts, thereby providing a permissive neural tone for insulin release under conditions of nutrient surplus. Unexpectedly, Insulin acts on the same upstream inhibitory neurons to conversely increase synapse number, hence re-instating negative tone. Our results suggest that two surplus-sensing hormonal systems, Leptin/Upd2 and Insulin, converge on a neuronal circuit with opposing outcomes that establish tonic, energy-store-dependent neuron activity.HighlightsThe adipokine Upd2 regulates number of inhibitory synaptic contacts on Insulin neurons.Upd2 activates an actin-regulating complex of Arouser, Basigin, and Gelsolin in target neurons.Arouser, Basigin, and Gelsolin reduce the extent of inhibitory contact on Insulin neurons.Insulin resets negative tone by increasing the number of synaptic contacts made by its own upstream inhibitory neurons.

Universal Qudit Hamiltonians

Communications in Mathematical Physics ◽

10.1007/s00220-021-03940-3 ◽

2021 ◽

Author(s):

Stephen Piddock ◽

Ashley Montanaro

Keyword(s):

State Energy ◽

Entangled State ◽

Quantum Computers ◽

List Type ◽

Universal Family ◽

Finite Dimensional ◽

Universal Quantum ◽

Aklt Model ◽

Almost All ◽

Natural Way

AbstractA family of quantum Hamiltonians is said to be universal if any other finite-dimensional Hamiltonian can be approximately encoded within the low-energy space of a Hamiltonian from that family. If the encoding is efficient, universal families of Hamiltonians can be used as universal analogue quantum simulators and universal quantum computers, and the problem of approximately determining the ground-state energy of a Hamiltonian from a universal family is QMA-complete. One natural way to categorise Hamiltonians into families is in terms of the interactions they are built from. Here we prove universality of some important classes of interactions on qudits (d-level systems): We completely characterise the k-qudit interactions which are universal, if augmented with arbitrary Hermitian 1-local terms. We find that, for all $$k \geqslant 2$$ k ⩾ 2 and all local dimensions $$d \geqslant 2$$ d ⩾ 2 , almost all such interactions are universal aside from a simple stoquastic class. We prove universality of generalisations of the Heisenberg model that are ubiquitous in condensed-matter physics, even if free 1-local terms are not provided. We show that the SU(d) and SU(2) Heisenberg interactions are universal for all local dimensions $$d \geqslant 2$$ d ⩾ 2 (spin $$\geqslant 1/2$$ ⩾ 1 / 2 ), implying that a quantum variant of the Max-d-Cut problem is QMA-complete. We also show that for $$d=3$$ d = 3 all bilinear-biquadratic Heisenberg interactions are universal. One example is the general AKLT model. We prove universality of any interaction proportional to the projector onto a pure entangled state.

Transient dopamine neuron activity precedes and encodes the vigor of contralateral movements

10.1101/2021.04.20.440527 ◽

2021 ◽

Author(s):

Marcelo D Mendonça ◽

Joaquim Alves da Silva ◽

Ledia F. Hernandez ◽

Ivan Castela ◽

José Obeso ◽

...

Keyword(s):

Substantia Nigra ◽

Dopamine Neurons ◽

Substantia Nigra Pars Compacta ◽

Neuron Activity ◽

Similar Proportion ◽

List Type ◽

Dopamine Depletion ◽

Movement Initiation ◽

Transient Activity ◽

Forelimb Movement

SummaryDopamine neurons (DANs) in the substantia nigra pars compacta (SNc) have been related to movement vigor, and loss of these neurons leads to bradykinesia in Parkinson’s disease. However, it remains unclear whether DANs encode a general motivation signal or modulate movement kinematics. We imaged activity of SNc DANs in mice trained in a novel operant task which relies on individual forelimb movement sequences. We uncovered that a similar proportion of SNc DANs increased their activity before ipsi- vs. contralateral forelimb movements. However, the magnitude of this activity was higher for contralateral actions, and was related to contralateral but not ipsilateral action vigor. In contrast, the activity of reward-related DANs, largely distinct from those modulated by movement, was not lateralized. Finally, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor. These results indicate that movement-initiation DANs encode more than a general motivation signal, and invigorate kinematic aspects of contralateral movements.HighlightsDeveloped a freely-moving task where mice learn rapid individual forelimb sequences.Movement-related DANs encode contralateral but not ipsilateral action vigor.The activity of reward-related DANs is not lateralized.Unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.eTOC summary: Mendonça et al. show that transient activity in movement-related dopamine neurons in substantia nigra pars compacta encodes contralateral, but not ipsilateral action vigor. Consistently, unilateral dopamine depletion impaired contralateral, but not ipsilateral, movement vigor.

Subanesthetic ketamine reactivates adult cortical plasticity to restore vision from amblyopia

10.1101/2020.03.16.994475 ◽

2020 ◽

Author(s):

Steven F. Grieco ◽

Xin Qiao ◽

Xiaoting Zheng ◽

Yongjun Liu ◽

Lujia Chen ◽

...

Keyword(s):

Functional Recovery ◽

Neural Plasticity ◽

Cortical Plasticity ◽

Brain Plasticity ◽

Excitatory Input ◽

Inhibitory Neurons ◽

List Type ◽

Visual Cortical

SummarySubanesthetic ketamine evokes rapid and long-lasting antidepressant effects in human patients. The mechanism for ketamine’s effects remains elusive, but ketamine may broadly modulate brain plasticity processes. We show that single-dose ketamine reactivates adult mouse visual cortical plasticity and promotes functional recovery of visual acuity defects from amblyopia. Ketamine specifically induces down-regulation of neuregulin-1 (NRG1) expression in parvalbumin-expressing (PV) inhibitory neurons in mouse visual cortex. NRG1 downregulation in PV neurons co-tracks both the fast onset and sustained decreases in synaptic inhibition to excitatory neurons, along with reduced synaptic excitation to PV neurons in vitro and in vivo following a single ketamine treatment. These effects are blocked by exogenous NRG1 as well as PV targeted receptor knockout. Thus ketamine reactivation of adult visual cortical plasticity is mediated through rapid and sustained cortical disinhibition via downregulation of PV-specific NRG1 signaling. Our findings reveal the neural plasticity-based mechanism for ketamine-mediated functional recovery from adult amblyopia.Highlights○ Disinhibition of excitatory cells by ketamine occurs in a fast and sustained manner○ Ketamine evokes NRG1 downregulation and excitatory input loss to PV cells○ Ketamine induced plasticity is blocked by exogenous NRG1 or its receptor knockout○ PV inhibitory cells are the initial functional locus underlying ketamine’s effects

Morphological diversity and connectivity of hippocampal interneurons

Cell and Tissue Research ◽

10.1007/s00441-018-2882-2 ◽

2018 ◽

Vol 373 (3) ◽

pp. 619-641 ◽

Cited By ~ 37

Author(s):

Sam A. Booker ◽

Imre Vida

Keyword(s):

Morphological Diversity ◽

Inhibitory Neurons ◽

Mammalian Brain ◽

Neuronal Function ◽

Principal Cells ◽

Axon Terminals ◽

Efferent Connections ◽

Rich Diversity ◽

A Cell ◽

The Rich

Abstract The mammalian forebrain is constructed from ensembles of neurons that form local microcircuits giving rise to the exquisite cognitive tasks the mammalian brain can perform. Hippocampal neuronal circuits comprise populations of relatively homogenous excitatory neurons, principal cells and exceedingly heterogeneous inhibitory neurons, the interneurons. Interneurons release GABA from their axon terminals and are capable of controlling excitability in every cellular compartment of principal cells and interneurons alike; thus, they provide a brake on excess activity, control the timing of neuronal discharge and provide modulation of synaptic transmission. The dendritic and axonal morphology of interneurons, as well as their afferent and efferent connections within hippocampal circuits, is central to their ability to differentially control excitability, in a cell-type- and compartment-specific manner. This review aims to provide an up-to-date compendium of described hippocampal interneuron subtypes, with respect to their morphology, connectivity, neurochemistry and physiology, a full understanding of which will in time help to explain the rich diversity of neuronal function.

Diminished cortical excitation and elevated inhibition during perceptual impairments in a mouse model of autism

10.1101/657189 ◽

2019 ◽

Author(s):

Joseph Del Rosario ◽

Anderson Speed ◽

Hayley Arrowood ◽

Cara Motz ◽

Machelle Pardue ◽

...

Keyword(s):

Visual Perception ◽

Mouse Model ◽

Inhibitory Activity ◽

Autism Spectrum ◽

Inhibitory Neurons ◽

Neuron Activity ◽

Conflicting Evidence ◽

Inhibitory Population ◽

Sensory Activity ◽

Speed Accuracy

AbstractSensory impairments are a core feature of autism spectrum disorder (ASD). These impairments affect visual perception (Robertson and Baron-Cohen, 2017), and have been hypothesized to arise from imbalances in cortical excitatory and inhibitory activity (Rubenstein and Merzenich, 2003; Nelson and Valakh, 2015; Sohal and Rubenstein, 2019); however, there is little direct evidence testing this hypothesis in identified excitatory and inhibitory neurons during impairments of sensory perception. Several recent studies have examined cortical activity in transgenic mouse models of ASD (Goel et al., 2018; Antoine et al., 2019; Lazaro et al., 2019), but have provided conflicting evidence for excitatory versus inhibitory activity deficits. Here, we utilized a genetically relevant mouse model of ASD (CNTNAP2−/− knockout, KO; Arking et al., 2008; Penagarikano et al., 2011) and directly recorded putative excitatory and inhibitory population spiking in primary visual cortex (V1) while measuring visual perceptual behavior (Speed et al., 2019). We found quantitative impairments in the speed, accuracy, and contrast sensitivity of visual perception in KO mice. These impairments were simultaneously associated with elevated inhibitory and diminished excitatory neuron activity evoked by visual stimuli during behavior, along with aberrant 3 – 10 Hz oscillations in superficial cortical layers 2/3 (L2/3). These results establish that perceptual deficits relevant for ASD can arise from diminished sensory activity of excitatory neurons in feedforward layers of cortical circuits.

Presynaptic inhibition of cutaneous afferents prevents self-generated itch

10.1101/806976 ◽

2019 ◽

Author(s):

Augusto Escalante ◽

Rüdiger Klein

Keyword(s):

Wide Spectrum ◽

Inhibitory Neurons ◽

Cutaneous Afferents ◽

List Type ◽

Spinal Neurons ◽

Skin Sensitivity ◽

Gastrin Releasing Peptide ◽

Hairy Skin ◽

Chronic Itch ◽

Excessive Grooming

SummaryChronic itch represents an incapacitating burden on patients suffering a wide spectrum of diseases. Despite recent advances in our understanding of the cells and circuits implicated in the processing of itch information, chronic itch often presents itself without apparent cause. Here, we identify a spinal subpopulation of inhibitory neurons defined by the expression of Ptf1a involved in gating mechanosensory information self-generated during movement. These neurons receive tactile and motor input and establish presynaptic inhibitory contacts on mechanosensory afferents. Loss of Ptf1a neurons leads to increased hairy skin sensitivity and chronic itch, at least partially mediated through the classic itch pathway involving gastrin releasing peptide receptor (GRPR) spinal neurons. Conversely, chemogenetic activation of GRPR neurons elicits itch which is suppressed by concomitant activation of Ptf1a neurons. These findings shed new light on the circuit mechanisms implicated in chronic itch and open novel targets for therapy developments.Highlights*Ptf1a specifies adult spinal presynaptic neurons contacting cutaneous afferents*Loss of spinal Ptf1a+ neurons leads to self-generated itch and excessive grooming*Absence of Ptf1a+ neurons increases hairy skin sensitivity which triggers scratching*GRPR+ neurons act downstream of Ptf1a+ neurons in spontaneous itch

Primary visual cortex injury produces loss of inhibitory neurons and long-term visual circuit dysfunction

10.1101/2020.08.19.258335 ◽

2020 ◽

Author(s):

Jan C. Frankowski ◽

Andrzej T. Foik ◽

Jiana R. Machhor ◽

David C. Lyon ◽

Robert F. Hunt

Keyword(s):

Visual Cortex ◽

Primary Visual Cortex ◽

Traumatic Injury ◽

Cortical Inhibition ◽

Inhibitory Neurons ◽

List Type ◽

V1 Neurons ◽

Adult Mice ◽

Brain Injured ◽

The Impact

SummaryPrimary sensory areas of the mammalian neocortex have a remarkable degree of plasticity, allowing neural circuits to adapt to dynamic environments. However, little is known about the effect of traumatic brain injury on visual system function. Here we applied a mild focal contusion injury to primary visual cortex (V1) in adult mice. We found that, although V1 was largely intact in brain-injured mice, there was a reduction in the number of inhibitory interneurons that extended into deep cortical layers. In general, we found a preferential reduction of interneurons located in superficial layers, near the impact site, while interneurons positioned in deeper layers were better preserved. Three months after injury, V1 neurons showed dramatically reduced responses to visual stimuli and weaker orientation selectivity and tuning, consistent with the loss of cortical inhibition. Our results demonstrate that V1 neurons no longer robustly and stably encode visual input following a mild traumatic injury.HighlightsInhibitory neurons are lost throughout brain injured visual cortexVisually-evoked potentials are severely degraded after injuryInjured V1 neurons show weaker selectivity and tuning consistent with reduced interneurons

Extracellular S100B alters spontaneous Ca2+ fluxes in dopaminergic neurons via L-type voltage gated calcium channels: Implications for Parkinson’s disease

10.1101/2021.02.24.432751 ◽

2021 ◽

Author(s):

Eric A. Bancroft ◽

Gauri Pandey ◽

Sara M. Zarate ◽

Rahul Srinivasan

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopaminergic Neurons ◽

Fold Increase ◽

Calcium Flux ◽

Substantia Nigra Pars Compacta ◽

Neuron Activity ◽

List Type ◽

Voltage Gated ◽

Midbrain Neurons

AbstractParkinson’s disease (PD) is associated with an abnormal increase in S100B within the midbrain and cerebrospinal fluid. In addition, overexpression of S100B in mice accelerates the loss of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons, suggesting a role for this protein in PD pathogenesis. We found that in the mouse SNc, S100B labeled astrocytic processes completely envelop the somata of tyrosine hydroxylase (TH) positive DA neurons. Based on this finding, we rationalized that abnormal increases in extracellularly secreted S100B by astrocytic processes in the SNc could alter DA neuron activity, thereby causing dysregulated midbrain function. To test this hypothesis, we measured the effect of bath perfused S100B peptide on the frequency and amplitude of spontaneous calcium fluxes in identified TH+ and TH− midbrain neurons from 3-week old mouse primary midbrain cultures. Acute exposure to 50 pM S100B caused a 2-fold increase in calcium flux frequency only in TH+ DA neurons. The L-type voltage gated calcium channel (VGCC) inhibitor, diltiazem eliminated S100B-mediated increases in DA neuron calcium flux frequency, while the T-type specific VGCC blocker mibefradil failed to inhibit the stimulatory effect of S100B. Chronic exposure to S100B caused a 3-fold reduction in calcium flux frequencies of TH+ neurons and also reduced calcium flux amplitudes in TH− neurons by ∼4-fold. Together, our results suggest that exposure to S100B pathologically alters spontaneous calcium activity in midbrain neurons via an extracellular mechanism involving L-type VGCCs expressed in DA neurons. These findings are relevant to understanding mechanisms underlying DA neuron loss during PD.Table of Contents ImageMain PointsExtracellular S100B increases Ca2+ fluxes in dopaminergic neuronsL-type VGCCs in dopaminergic neurons are required for S100B-mediated increases in Ca2+ fluxesChronic S100B alters Ca2+ fluxes in dopaminergic and non-dopaminergic neurons

A kernel-based method to calculate local field potentials from networks of spiking neurons

10.1101/2020.03.29.014654 ◽

2020 ◽

Cited By ~ 2

Author(s):

Bartosz Telenczuk ◽

Maria Telenczuk ◽

Alain Destexhe

Keyword(s):

Local Field ◽

Pyramidal Neurons ◽

Field Potential ◽

Point Of View ◽

Spiking Neurons ◽

Inhibitory Neurons ◽

List Type ◽

Synaptic Currents ◽

Hippocampal Pyramidal Neurons ◽

Low Pass

AbstractBackgroundThe local field potential (LFP) is usually calculated from current sources arising from transmembrane currents, in particular in asymmetric cellular morphologies such as pyramidal neurons.New methodHere, we adopt a different point of view and relate the spiking of neurons to the LFP through efferent synaptic connections and provide a method to calculate LFPs.ResultsWe show that the so-called unitary LFPs (uLFP) provide the key to such a calculation. We show experimental measurements and simulations of uLFPs in neocortex and hippocampus, for both excitatory and inhibitory neurons. We fit a “kernel” function to measurements of uLFPs, and we estimate its spatial and temporal spread by using simulations of morphologically detailed reconstructions of hippocampal pyramidal neurons. Assuming that LFPs are the sum of uLFPs generated by every neuron in the network, the LFP generated by excitatory and inhibitory neurons can be calculated by convolving the trains of action potentials with the kernels estimated from uLFPs. This provides a method to calculate the LFP from networks of spiking neurons, even for point neurons for which the LFP is not easily defined. We show examples of LFPs calculated from networks of point neurons and compare to the LFP calculated from synaptic currents.ConclusionsThe kernel-based method provides a practical way to calculate LFPs from networks of point neurons.HighlightsWe provide a method to estimate the LFP from spiking neuronsThis method is based on kernels, estimated from experimental dataWe show applications of this method to calculate the LFP from networks of spiking neuronsWe show that the kernel-based method is a low-pass filtered version of the LFP calculated from synaptic currents

Post-ictal generalized EEG suppression and seizure-induced mortality are reduced by enhancing dorsal raphe serotonergic neurotransmission

10.1101/2020.06.28.172460 ◽

2020 ◽

Author(s):

Alexandra N. Petrucci ◽

Katelyn G. Joyal ◽

Jonathan W. Chou ◽

Rui Li ◽

Kimberly M. Vencer ◽

...

Keyword(s):

Dorsal Raphe Nucleus ◽

Nrem Sleep ◽

Dorsal Raphe ◽

Raphe Nucleus ◽

Neuron Activity ◽

Maximal Electroshock ◽

List Type ◽

Unexpected Death ◽

Dorsal Raphé ◽

Stimulation Of

AbstractSudden unexpected death in epilepsy (SUDEP) is the leading cause of death in patients with refractory epilepsy. A proposed risk marker for SUDEP is the duration of post-ictal generalized EEG suppression (PGES). The mechanisms underlying PGES are unknown. Serotonin (5-HT) has been implicated in SUDEP pathophysiology. Seizures suppress activity of 5-HT neurons in the dorsal raphe nucleus (DRN). We hypothesized that suppression of DRN 5-HT neuron activity contributes to PGES and increasing 5-HT neurotransmission or stimulating the DRN before a seizure would decrease PGES duration. Adult C57BL/6 and Pet1-Cre mice received EEG/EMG electrodes, a bipolar stimulating/recording electrode in the right basolateral amygdala, and either a microdialysis guide cannula or an injection of adeno-associated virus (AAV) allowing expression of channelrhodopsin2 plus an optic fiber into the DRN. Systemic application of the selective 5-HT reuptake inhibitor citalopram (20 mg/kg) decreased PGES duration from seizures induced during wake (n = 23) and NREM sleep (n = 13) whereas fluoxetine (20 mg/kg) pretreatment decreased PGES duration following seizures induced from wake (n = 11), but not NREM sleep (n = 9). Focal chemical (n = 6) or optogenetic (n = 8) stimulation of the DRN reduced PGES duration following kindled seizures and reduced morality following maximal electroshock seizures (n = 6) induced during wake. During PGES, animals exhibited immobility and suppression of EEG activity that was reduced by citalopram pretreatment. These results indicate that 5-HT and the DRN may regulate PGES and seizure-induced mortality.Highlights-PGES consistently follows seizures induced by amygdala stimulation in amygdala-kindled mice.-Seizure-induced dysregulation of 5-HT neurotransmission from the dorsal raphe nucleus may contribute to PGES.-Systemic administration of 5-HT enhancing drugs and stimulation of the DRN reduces PGES duration.-PGES is associated with post-ictal immobility in kindled mice that can be reduced by pretreatment with citalopram.-Recovery of EEG frequencies to baseline occurs in a stepwise manner with the lowest frequencies recovering first.