scholarly journals Ultra-sparse connectivity within the lateral hypothalamus

2020 ◽  
Author(s):  
Denis Burdakov ◽  
Mahesh M. Karnani
Keyword(s):  
Lateral Hypothalamus ◽  
Brain Slices ◽  
Brain Structures ◽  
Gamma Oscillations ◽  
Local Network ◽  
Excitatory Synapses ◽  
Neuronal Populations ◽  
Reward Seeking ◽  
Intrinsic Connectivity ◽  
Sparse Connectivity

AbstractThe lateral hypothalamus (LH) contains neuronal populations which generate fundamental behavioural actions such as feeding, sleep, movement, attack and evasion. Their activity is also correlated with various appetitive and consummatory behaviours as well as reward seeking. It is unknown how neural activity within and among these populations is coordinated. One hypothesis postulates that they communicate using inhibitory and excitatory synapses, forming local microcircuits. We inspected this hypothesis using quadruple whole cell recordings and optogenetics to screen thousands of potential connections in brain slices. In contrast to the neocortex, we found near zero connectivity within the LH. In line with its ultra-sparse intrinsic connectivity, we found that the LH does not generate local beta and gamma oscillations. This suggests that LH neurons integrate incoming input within individual neurons rather than through local network interactions, and that input from other brain structures is decisive for selecting active populations in LH.

scholarly journals Electrophysiological characterization and MCH/orexin neuronal distribution in the lateral hypothalamus of naked mole-rats (Heterocephalus glaber)

2018 ◽  
Author(s):  
Zoé Husson ◽  
John Apergis-Schoute ◽  
Ewan St John Smith
Keyword(s):  
Lateral Hypothalamus ◽  
Mammalian Species ◽  
Brain Slices ◽  
Heterocephalus Glaber ◽  
Electrophysiological Properties ◽  
Neuronal Populations ◽  
Hypothalamic Function ◽  
Extreme Longevity ◽  
Neuronal Distribution ◽  
Electrophysiological Characterization

AbstractThe lateral hypothalamus (LH) controls various homeostatic processes, including sleep-wake cycles, energy balance and thermoregulation in many mammalian species. In the LH, melanin-concentrating hormone (MCH) and hypocretin/orexin (HO) containing neurons differentially regulate these processes. Naked mole-rats (NMR) (Heterocephalus glaber) are eusocial mammals with remarkable physiological peculiarities including extreme longevity without significant weight gain and absence of thermoregulation. Altered hypothalamic function could potentially underlie the unusual NMR phenotypes, but to date electrophysiological characterization of LH NMR neurons and expression of MCH and HO is missing. Here, we performed whole-cell recordings from LH neurons in acute NMR and mouse brain slices and found that NMR and mouse neuronal basic properties and activities were comparable. Additionally, we showed that both MCH-positive and HO-positive neuronal populations exist in the NMR hypothalamus and although the majority of MCH- and HO-positive neurons are located in the LH, as previously described in rodents, significant differences exist in MCH/HO distribution in other NMR hypothalamic areas. These results indicate that NMR LH neurons are comparable to mouse neurons with respect to their electrophysiological properties, but differences in the neuronal MCH and HO populations in hypothalamic regions exist and may contribute to the adaptive changes seen in NMR homeostatic processes.

scholarly journals Evidence that PV+ cells enhance temporal population codes but not stimulus-related timing in auditory cortex

2017 ◽  
Author(s):  
Bryan M. Krause ◽  
Caitlin A. Murphy ◽  
Daniel J. Uhlrich ◽  
Matthew I. Banks
Keyword(s):  
Brain Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Cortical Activity ◽  
Spike Timing ◽  
Network Activity ◽  
Local Network ◽  
Network Bursts ◽  
Spatio Temporal

AbstractSpatio-temporal cortical activity patterns relative to both peripheral input and local network activity carry information about stimulus identity and context. GABAergic interneurons are reported to regulate spiking at millisecond precision in response to sensory stimulation and during gamma oscillations; their role in regulating spike timing during induced network bursts is unclear. We investigated this issue in murine auditory thalamo-cortical (TC) brain slices, in which TC afferents induced network bursts similar to previous reports in vivo. Spike timing relative to TC afferent stimulation during bursts was poor in pyramidal cells and SOM+ interneurons. It was more precise in PV+ interneurons, consistent with their reported contribution to spiking precision in pyramidal cells. Optogenetic suppression of PV+ cells unexpectedly improved afferent-locked spike timing in pyramidal cells. In contrast, our evidence suggests that PV+ cells do regulate the spatio-temporal spike pattern of pyramidal cells during network bursts, whose organization is suited to ensemble coding of stimulus information. Simulations showed that suppressing PV+ cells reduces the capacity of pyramidal cell networks to produce discriminable spike patterns. By dissociating temporal precision with respect to a stimulus versus internal cortical activity, we identified a novel role for GABAergic cells in regulating information processing in cortical networks.

scholarly journals Moderately Inducing Autophagy Reduces Tertiary Brain Injury after Perinatal Hypoxia-Ischemia

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 898
Author(s):  
Brian H. Kim ◽  
Maciej Jeziorek ◽  
Hur Dolunay Kanal ◽  
Viorica Raluca Contu ◽  
Radek Dobrowolski ◽  
...  
Keyword(s):  
Cell Death ◽  
Structural Integrity ◽  
Transforming Growth Factor ◽  
Ex Vivo ◽  
Brain Slices ◽  
Brain Structures ◽  
Improved Outcomes ◽  
Hypoxia Ischemia ◽  
Tgfβ Receptor ◽  
Progressive Neurodegeneration

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5)—SB505124—three days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated light chain 3 (LC3), a key protein known to mediate autophagy. However, those studies did not determine whether (1) SB was acting directly on the CNS and (2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist three days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting three days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.

scholarly journals Glutamatergic and GABAergic neuronal populations in the dorsolateral Periacqueductual Gray have different functional roles in fear conditioning

2019 ◽  
Author(s):  
Quentin Montardy ◽  
Zheng Zhou ◽  
Xuemei Liu ◽  
Zhuogui Lei ◽  
Pengyu Zeng ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Brain Structures ◽  
Aversive Stimulation ◽  
Emotional States ◽  
Functional Roles ◽  
Neuronal Populations ◽  
Defensive Behaviors ◽  
A Cell ◽  
Midbrain Structure ◽  
Virus Tracing

AbstractIt is though that only a subset of brain structures can encode emotional states. This can be investigated though a set of properties, including the ability of neurons to respond to a conditioned stimulus (CS) preceding an aversive unconditioned stimulus (US). The dorsolateral periacqueductal gray (dPAG) is a midbrain structure though to have an essential role in coordinating defensive behaviors in response to aversive stimulation. But its ability of dPAG neurons to encode a CS following fear conditioning as not been sufficiently studied.Here we used calcium imaging by fiber photometry to record the activity of dPAGVGluT2+ and dPAGGAD2+ neuronal populations during unconditioned and conditioned aversive stimulation. Then, following an unconditioned stimulation we performed a retrieval experiment to quantify memory-like responses of dPAG neurons. This shown that whilst both dPAGVGluT2+ and dPAGGAD2+ neuronal populations respond to direct US stimulation, and to CS stimulation during conditioning, only the dPAGVGluT2+ population persisted in responding to the CS stimulation during retrieval. Finally, to better understand dPAGVGluT2+ and dPAGGAD2+ connectivity patterns, we performed a cell specific monosynaptic retrograde rabies virus tracing experiment. This revealed that different patterns of fibers projects to dPAGVGluT2+ and dPAGGAD2+, further complementing our recording showing divergences between PAGVGluT2+ and dPAGGAD2+ populations.

scholarly journals A neural circuit for gamma-band coherence across the retinotopic map in mouse visual cortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Richard Hakim ◽  
Kiarash Shamardani ◽  
Hillel Adesnik
Keyword(s):  
Visual Cortex ◽  
Neural Circuit ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Gamma Oscillations ◽  
Gamma Band ◽  
Neuron Activity ◽  
Mouse Visual Cortex ◽  
Retinotopic Map

Cortical gamma oscillations have been implicated in a variety of cognitive, behavioral, and circuit-level phenomena. However, the circuit mechanisms of gamma-band generation and synchronization across cortical space remain uncertain. Using optogenetic patterned illumination in acute brain slices of mouse visual cortex, we define a circuit composed of layer 2/3 (L2/3) pyramidal cells and somatostatin (SOM) interneurons that phase-locks ensembles across the retinotopic map. The network oscillations generated here emerge from non-periodic stimuli, and are stimulus size-dependent, coherent across cortical space, narrow band (30 Hz), and depend on SOM neuron but not parvalbumin (PV) neuron activity; similar to visually induced gamma oscillations observed in vivo. Gamma oscillations generated in separate cortical locations exhibited high coherence as far apart as 850 μm, and lateral gamma entrainment depended on SOM neuron activity. These data identify a circuit that is sufficient to mediate long-range gamma-band coherence in the primary visual cortex.

scholarly journals Dopaminergic Modulation of Local Network Activity in Rat Prefrontal Cortex

2007 ◽  
Vol 97 (6) ◽  
pp. 4120-4128 ◽  
Author(s):  
Susanta Bandyopadhyay ◽  
John J. Hablitz
Keyword(s):  
Prefrontal Cortex ◽  
Synaptic Transmission ◽  
Receptor Agonist ◽  
Neuronal Networks ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Network Activity ◽  
Lateral Spread ◽  
Local Network ◽  
Evoked Activity

Dopamine modulates prefrontal cortex excitability in complex ways. Dopamine's net effect on local neuronal networks is therefore difficult to predict based on studies on pharmacologically isolated excitatory or inhibitory connections. In the present work, we have studied the effects of dopamine on evoked activity in acute rat brain slices when both excitation and inhibition are intact. Whole cell recordings from layer II/III pyramidal cells under conditions of normal synaptic transmission showed that bath-applied dopamine (30 μM) increased the outward inhibitory component of composite postsynaptic currents, whereas inward excitatory currents were not significantly affected. Optical imaging with the voltage-sensitive dye N-(3-(triethylammonium)propyl)-4-(4-(p-diethylaminophenyl)buta-dienyl)pyridinium dibromide revealed that bath application of dopamine significantly decreased the amplitude, duration, and lateral spread of activity in local cortical networks. This effect of dopamine was observed both with single and train (5 at 20 Hz) stimuli. The effect was mimicked by the D1-like receptor agonist R(+)-6-chloro-7,8-dihydroxy-1-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (1 μM) and was blocked by R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (10 μM), a selective antagonist for D1-like receptors. The D2-like receptor agonist quinpirole (10 μM) had no significant effect on evoked dye signals. Our results suggest that dopamine's effect on inhibition dominates over that on excitation under conditions of normal synaptic transmission. Such neuromodulation by dopamine may be important for maintenance of stability in local neuronal networks in the prefrontal cortex.

scholarly journals Brain metabolism modulates neuronal excitability in a mouse model of pyruvate dehydrogenase deficiency

2019 ◽  
Vol 11 (480) ◽  
pp. eaan0457 ◽  
Author(s):  
Vikram Jakkamsetti ◽  
Isaac Marin-Valencia ◽  
Qian Ma ◽  
Levi B. Good ◽  
Tyler Terrill ◽  
...  
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Brain Metabolism ◽  
Neuronal Excitability ◽  
Oscillation Amplitude ◽  
Brain Slices ◽  
Tca Cycle ◽  
Gamma Oscillations ◽  
Epileptiform Discharges ◽  
Discharge Duration

Glucose is the ultimate substrate for most brain activities that use carbon, including synthesis of the neurotransmitters glutamate and γ-aminobutyric acid via mitochondrial tricarboxylic acid (TCA) cycle. Brain metabolism and neuronal excitability are thus interdependent. However, the principles that govern their relationship are not always intuitive because heritable defects of brain glucose metabolism are associated with the paradoxical coexistence, in the same individual, of episodic neuronal hyperexcitation (seizures) with reduced basal cerebral electrical activity. One such prototypic disorder is pyruvate dehydrogenase (PDH) deficiency (PDHD). PDH is central to metabolism because it steers most of the glucose-derived flux into the TCA cycle. To better understand the pathophysiology of PDHD, we generated mice with brain-specific reduced PDH activity that paralleled salient human disease features, including cerebral hypotrophy, decreased amplitude electroencephalogram (EEG), and epilepsy. The mice exhibited reductions in cerebral TCA cycle flux, glutamate content, spontaneous, and electrically evoked in vivo cortical field potentials and gamma EEG oscillation amplitude. Episodic decreases in gamma oscillations preceded most epileptiform discharges, facilitating their prediction. Fast-spiking neuron excitability was decreased in brain slices, contributing to in vivo action potential burst prolongation after whisker pad stimulation. These features were partially reversed after systemic administration of acetate, which augmented cerebral TCA cycle flux, glutamate-dependent synaptic transmission, inhibition and gamma oscillations, and reduced epileptiform discharge duration. Thus, our results suggest that dysfunctional excitability in PDHD is consequent to reduced oxidative flux, which leads to decreased neuronal activation and impaired inhibition, and can be mitigated by an alternative metabolic substrate.

Engagement of Rat Striatal Neurons by Cortical Epileptiform Activity Investigated With Paired Recordings

2004 ◽  
Vol 92 (5) ◽  
pp. 2725-2737 ◽  
Author(s):  
Enrico Bracci ◽  
Diego Centonze ◽  
Giorgio Bernardi ◽  
Paolo Calabresi
Keyword(s):  
Cortical Neurons ◽  
Epileptiform Activity ◽  
Brain Slices ◽  
Brain Structures ◽  
Extracellular Potassium ◽  
Striatal Neurons ◽  
Cholinergic Interneurons ◽  
Medial Agranular Cortex ◽  
The Impact ◽  
Oblique Slices

The striatum is thought to play an important role in the spreading of epilepsy from cortical areas to deeper brain structures, but this issue has not been addressed with intracellular techniques. Paired recordings were used to assess the impact of cortical epileptiform activity on striatal neurons in brain slices. Bath-application of 4-amynopyridine (100 μM) and bicuculline (20 μM) induced synchronized bursts in all pairs of cortical neurons (≤5 mm apart) in coronal, sagittal, and oblique slices (which preserve connections from the medial agranular cortex to the striatum). Under these conditions, striatal medium spiny neurons (MSs) displayed a strong increased spontaneous glutamatergic activity. This activity was not correlated to the cortical bursts and was asynchronous in pairs of MSs. Sporadic, large-amplitude synchronous depolarizations also occurred in MSs. These events were simultaneously detected in glial cells, suggesting that they were accompanied by considerable increases in extracellular potassium. In oblique slices, cortically driven bursts were also observed in MSs. These events were synchronized to cortical epileptiform bursts, depended on non– N-methyl-d-aspartate (NMDA) glutamate receptors, and persisted in the cortex, but not in the striatum, after disconnection of the two structures. During these bursts, MS membrane potential shifted to a depolarized value (59 ± 4 mV) on which an irregular waveform, occasionally eliciting spikes, was superimposed. Thus synchronous activation of a limited set of corticostriatal afferents can powerfully control MSs. Cholinergic interneurons located <120 μm from simultaneously recorded MSs, did not display cortically driven bursts, suggesting that these cells are much less easily engaged by cortical epileptiform activity.

scholarly journals A New Method to Measure Brain Serotonin Synthesis in vivo. I. Theory and Basic Data for a Biological Model

1990 ◽  
Vol 10 (1) ◽  
pp. 1-12 ◽  
Author(s):  
M. Diksic ◽  
S. Nagahiro ◽  
T. L. Sourkes ◽  
Y. L. Yamamoto
Keyword(s):  
Trichloroacetic Acid ◽  
Brain Slices ◽  
Brain Structures ◽  
Pineal Body ◽  
Biological Model ◽  
Tracer Kinetics ◽  
Serotonin Synthesis ◽  
Precursor Pool ◽  
The Brain

We describe here an autoradiographic method to measure the in vivo rate of serotonin synthesis in rat brain. The method is based on the use of the l-tryptophan analogue a-methyl-l-tryptophan ( a-MTrp), which is converted in vivo into a-methylserotonin ( a-M5HT). Since a-M5HT is not a substrate for monoamine oxidase, it is accumulated in the brain tissue. Data are presented to confirm time-dependent conversion of a-MTrp into a-M5HT in the dorsal raphe nucleus and also in the pineal body, an organ outside the blood–brain barrier. It has also been shown that washing brain slices in 10% trichloroacetic acid results in <3% incorporation of a-MTrp into brain proteins. The rates of synthesis are calculated in several grossly dissected brain structures by using tracer kinetics and a three-compartment biological model. The half-life of the precursor pool is estimated to be ∼20 min. The rate of serotonin synthesis is highest in the pineal body.

scholarly journals Local network regulation of orexin neurons in the lateral hypothalamus

2011 ◽  
Vol 301 (3) ◽  
pp. R572-R580 ◽  
Author(s):  
Julia Burt ◽  
Christian O. Alberto ◽  
Matthew P. Parsons ◽  
Michiru Hirasawa
Keyword(s):  
Energy Balance ◽  
Lateral Hypothalamus ◽  
Feedback Regulation ◽  
Modern Society ◽  
Fine Tuning ◽  
Local Network ◽  
Cellular Mechanisms ◽  
Negative Feedback Regulation ◽  
Common Causes ◽  
Melanin Concentrating Hormone

Obesity and inadequate sleep are among the most common causes of health problems in modern society. Thus, the discovery that orexin (hypocretin) neurons play a pivotal role in sleep/wake regulation, energy balance, and consummatory behaviors has sparked immense interest in understanding the regulatory mechanisms of these neurons. The local network consisting of neurons and astrocytes within the lateral hypothalamus and perifornical area (LH/PFA), where orexin neurons reside, shapes the output of orexin neurons and the LH/PFA. Orexin neurons not only send projections to remote brain areas but also contribute to the local network where they release multiple neurotransmitters to modulate its activity. These neurotransmitters have opposing actions, whose balance is determined by the amount released and postsynaptic receptor desensitization. Modulation and negative feedback regulation of excitatory glutamatergic inputs as well as release of astrocyte-derived factors, such as lactate and ATP, can also affect the excitability of orexin neurons. Furthermore, distinct populations of LH/PFA neurons express neurotransmitters with known electrophysiological actions on orexin neurons, such as melanin-concentrating hormone, corticotropin-releasing factor, thyrotropin-releasing hormone, neurotensin, and GABA. These LH/PFA-specific mechanisms may be important for fine tuning the firing activity of orexin neurons to maintain optimal levels of prolonged output to sustain wakefulness and stimulate consummatory behaviors. Building on these exciting findings should shed further light onto the cellular mechanisms of energy balance and sleep-wake regulation.

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