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 Basolateral amygdala neurons are activated during threat expectation

2019 ◽  
Vol 121 (5) ◽  
pp. 1761-1777 ◽  
Author(s):  
Alon Amir ◽  
Pinelopi Kyriazi ◽  
Seung-Chan Lee ◽  
Drew B. Headley ◽  
Denis Paré
Keyword(s):  
Brain Stem ◽  
Fear Conditioning ◽  
Linear Model ◽  
Unit Activity ◽  
Generalized Linear Model ◽  
Basolateral Amygdala ◽  
Unit Recording ◽  
Lateral Amygdala ◽  
Defensive Behaviors ◽  
Foraging Task

Fear conditioning studies have led to the view that the amygdala contains neurons that signal threat and in turn elicit defensive behaviors through their brain stem and hypothalamic targets. In agreement with this model, a prior unit-recording study in rats performing a seminaturalistic foraging task revealed that many lateral amygdala (LA) neurons are predator responsive. In contrast, our previous study emphasized that most basolateral (BL) amygdala neurons are inhibited at proximity of the predator. However, the two studies used different methods to analyze unit activity, complicating comparisons between them. By applying the same method to the sample of BL neurons we recorded previously, the present study revealed that most principal cells are inhibited by the predator and only 4.5% are activated. Moreover, two-thirds of these cells were also activated by nonthreatening stimuli. In fact, fitting unit activity with a generalized linear model revealed that the only task variables associated with a prevalent positive modulation of BL activity were expectation of the predator’s presence and whether the prior trial had been a failure or success. At odds with the threat-coding model of the amygdala, actual confrontation with the predator was usually associated with a widespread inhibition of principal BL neurons. NEW & NOTEWORTHY The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are responsive to threats and that most of them are also activated by nonthreatening stimuli. Yet, expectation of the threat’s presence was associated with a prevalent positive modulation of BL activity; actual confrontation with the threat was associated with a widespread inhibition.

scholarly journals Functional Role of the PE Domain and Immunogenicity of the Mycobacterium tuberculosis Triacylglycerol Hydrolase LipY

2007 ◽  
Vol 76 (1) ◽  
pp. 127-140 ◽  
Author(s):  
Kanhu C. Mishra ◽  
Chantal de Chastellier ◽  
Yeddula Narayana ◽  
Pablo Bifani ◽  
Alistair K. Brown ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Humoral Response ◽  
Host Immune System ◽  
Functional Roles ◽  
Triacylglycerol Hydrolase ◽  
Immunodominant Antigen ◽  
Surface Localization ◽  
A Cell ◽  
First Time

ABSTRACT PE and PPE proteins appear to be important for virulence and immunopathogenicity in mycobacteria, yet the functions of the PE/PPE domains remain an enigma. To decipher the role of these domains, we have characterized the triacylglycerol (TAG) hydrolase LipY from Mycobacterium tuberculosis, which is the only known PE protein expressing an enzymatic activity. The overproduction of LipY in mycobacteria resulted in a significant reduction in the pool of TAGs, consistent with the lipase activity of this enzyme. Unexpectedly, this reduction was more pronounced in mycobacteria overexpressing LipY lacking the PE domain [LipY(ΔPE)], suggesting that the PE domain participates in the modulation of LipY activity. Interestingly, Mycobacterium marinum contains a protein homologous to LipY, termed LipYmar, in which the PE domain is substituted by a PPE domain. As for LipY, overexpression of LipYmar in Mycobacterium smegmatis significantly reduced the TAG pool, and this was further pronounced when the PPE domain of LipYmar was removed. Fractionation studies and Western blot analysis demonstrated that both LipY and LipY(ΔPE) were mainly present in the cell wall, indicating that the PE domain was not required for translocation to this site. Furthermore, electron microscopy immunolabeling of LipY(ΔPE) clearly showed a cell surface localization, thereby suggesting that the lipase may interact with the host immune system. Accordingly, a strong humoral response against LipY and LipY(ΔPE) was observed in tuberculosis patients. Together, our results suggest for the first time that both PE and PPE domains can share similar functional roles and that LipY represents a novel immunodominant antigen.

Behavioral Neuroscience of Circuits Involved in Fear Processing

2016 ◽  
Author(s):  
Elizabeth P. Bauer ◽  
Denis Paré
Keyword(s):  
Fear Conditioning ◽  
Post Traumatic Stress Disorder ◽  
Traumatic Stress ◽  
Current Knowledge ◽  
Brain Structures ◽  
Fear Learning ◽  
Post Traumatic Stress ◽  
Post Traumatic ◽  
The Brain ◽  
Insight Into

Normal fear regulation includes the ability to learn by experience that some circumstances predict danger. This process, which can be modeled in the laboratory using Pavlovian fear conditioning, appears to be disrupted in individuals with post-traumatic stress disorder (PTSD). Understanding of the mechanisms underlying fear learning has progressed tremendously in the last 25 years, and constitutes a promising paradigm to study the neural bases of PTSD. This chapter first reviews current knowledge of the brain structures involved in fear learning, expression and extinction, including the contributions of the amygdala and prefrontal cortex. It then addresses how these circuits are affected by PTSD and how fear processing is altered in PTSD. Understanding PTSD within a fear-conditioning and extinction framework provides insight into why certain individuals are susceptible to developing PTSD and suggests potential therapies.

scholarly journals Actions of a Pair of Identified Cerebral-Buccal Interneurons (CBI-8/9) in Aplysia That Contain the Peptide Myomodulin

1999 ◽  
Vol 81 (2) ◽  
pp. 507-520 ◽  
Author(s):  
Yuanpei Xin ◽  
Itay Hurwitz ◽  
Ray Perrins ◽  
Colin G. Evans ◽  
Vera Alexeeva ◽  
...  
Keyword(s):  
Cerebral Ganglion ◽  
Rhythmic Activity ◽  
Excitatory Input ◽  
Small Population ◽  
Inhibitory Input ◽  
Functional Roles ◽  
Buccal Mass ◽  
Strong Contraction ◽  
A Cell ◽  
To Receive

Actions of a pair of identified cerebral-buccal interneurons (CBI-8/9) in Aplysia that contain the peptide myomodulin. A combination of biocytin back-fills of the cerebral-buccal connectives and immunocytochemistry of the cerebral ganglion demonstrated that of the 13 bilateral pairs of cerebral-buccal interneurons in the cerebral ganglion, a subpopulation of 3 are immunopositive for the peptide myomodulin. The present paper describes the properties of two of these cells, which we have termed CBI-8 and CBI-9. CBI-8 and CBI-9 were found to be dye coupled and electrically coupled. The cells have virtually identical properties, and consequently we consider them to be “twin” pairs and refer to them as CBI-8/9. CBI-8/9 were identified by electrophysiological criteria and then labeled with dye. Labeled cells were found to be immunopositive for myomodulin, and, using high pressure liquid chromatography, the cells were shown to contain authentic myomodulin. CBI-8/9 were found to receive synaptic input after mechanical stimulation of the tentacles. They also received excitatory input from C-PR, a neuron involved in neck lengthening, and received a slow inhibitory input from CC5, a cell involved in neck shortening, suggesting that CBI-8/9 may be active during forward movements of the head or buccal mass. Firing of CBI-8 or CBI-9 resulted in the activation of a relatively small number of buccal neurons as evidenced by extracellular recordings from buccal nerves. Firing also produced local movements of the buccal mass, in particular a strong contraction of the I7 muscle, which mediates radula opening. CBI-8/9 were found to produce a slow depolarization and rhythmic activity of B48, the motor neuron for the I7 muscle. The data provide continuing evidence that the small population of cerebral buccal interneurons is composed of neurons that are highly diverse in their functional roles. CBI-8/9 may function as a type of premotor neuron, or perhaps as a peptidergic modulatory neuron, the functions of which are dependent on the coactivity of other neurons.

Features of the involvement of the dopamine and serotonin brain systems in positive and negative emotional states in rats

2020 ◽  
Vol 18 (2) ◽  
pp. 123-130
Author(s):  
Eugenii R. Bychkov ◽  
Andrei A. Lebedev ◽  
Nikolai S. Efimov ◽  
Artyem S. Kryukov ◽  
Inessa V. Karpova ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Lateral Hypothalamus ◽  
Treatment Strategies ◽  
Emotional Reactions ◽  
Aversive Stimulation ◽  
Male Rats ◽  
Emotional States ◽  
Neuropsychiatric Diseases ◽  
Self Stimulation ◽  
Stimulation Of

The aim was to study the effect of rewarding and aversive stimulation of lateral hypothalamus on the turnover of monoamines in the terminal structures of the mesocorticolimbic and nigrostriatal systems: the nucleus accumbens (NAc) and striatum (St). The Wistar male rats were implanted electrodes in the lateral hypothalamus and further trained in self-stimulation test. Animals were also selected on aversive emotional reactions were observed after pressing the pedal for self-stimulation. Subsequently, forced stimulation was performed for 5 minutes and the animals were decapitated. The content of norepinephrine, dopamine (DA) and its metabolites 3,4-dioxiphenylacetic acid (DOPАС) and homovanilinic acid, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens and striatum were determined by high performance liquid chromatography with electrochemical detection. Positive and aversive stimulation of lateral hypothalamus decreased the level of DA in the NAc, however, only stimulation of the positive emotiogenic zone increased the DA and 5-HT turnover in the NAc, as evidenced by an increase in the DOPАС/DA and 5-HIAA/SER ratios, respectively. Rewarding and aversive stimulation decreased the level of 5-HT in St, however, only rewarding stimulation decreased the St level of 5-HIAA compared to control and animals with aversive stimulation. Rewarding stimulation increased the turnover of serotonin in St, as evidenced by the increase of 5-HIAA/5-HT ratios. The activity of the noradrenergic system did not change after rewarding and aversive stimulation. Thus, both rewarding and aversive electrical stimulation increases the turnover of DA and 5-HT in NAc and St. However, these changes are more significant after rewarding stimulation. DA turnover increases more in NAc, and 5-HT turnover in St. The data obtained indicate the specificity of the dopaminergic and serotonergic involvement for the formation of a modality of emotional reactions. Data may provide guidance for developing treatment strategies for neuropsychiatric diseases related to the malfunction of the reward system.

Cell therapy in Huntington disease

2008 ◽  
Vol 24 (3-4) ◽  
pp. E9 ◽  
Author(s):  
Claire D. Clelland ◽  
Roger A. Barker ◽  
Colin Watts
Keyword(s):  
Cell Therapy ◽  
Huntington Disease ◽  
Neuronal Cell ◽  
Therapeutic Agents ◽  
Emotional Disturbances ◽  
Motor Impairments ◽  
Neuronal Populations ◽  
A Cell ◽  
Therapy Strategies ◽  
Dying Cells

✓ Huntington disease (HD), caused by polyglutamate expansions in the huntingtin protein, is a progressive neurodegenerative disease resulting in cognitive and motor impairments and death. Neuronal dysfunction and degeneration contribute to progressive physiological, motor, cognitive, and emotional disturbances characteristic of HD. A major impetus for research into the treatment of HD has centered on cell therapy strategies to protect vulnerable neuronal cell populations or to replace dysfunctional or dying cells. The work underlying 3 approaches to HD cell therapy includes the potential for self-repair through the manipulation of endogenous stem cells and/or neurogenesis, the use of fetal or stem cell transplantation as a cell replacement strategy, and the administration of neurotrophic factors to protect susceptible neuronal populations. These approaches have shown some promising results in animal models of HD. Although striatal transplantation of fetal-derived cells has undergone clinical assessment since the 1990s, many cell therapy strategies have yet to be applied in the clinic environment. A more thorough understanding of the pathophysiologies underlying HD as well as the response of both endogenous and exogenous cells to the degenerating brain will inform their merit as potential therapeutic agents and enhance the framework by which the success of such strategies are determined.

scholarly journals Induction of flight via midbrain projections to the cuneiform nucleus

2021 ◽  
Author(s):  
Emmy F Tsang ◽  
Camilla Orlandini ◽  
Rahul Sureka ◽  
Alvaro H Crevenna ◽  
Emerald Perlas ◽  
...  
Keyword(s):  
Escape Behavior ◽  
Periaqueductal Gray ◽  
Flight Behavior ◽  
Optogenetic Stimulation ◽  
Dorsal Periaqueductal Gray ◽  
Defensive Behaviors ◽  
Cuneiform Nucleus ◽  
Midbrain Structure

The dorsal periaqueductal gray is a midbrain structure implicated in the control of defensive behaviors and the processing of painful stimuli. Electrical stimulation or optogenetic activation of excitatory neurons in dorsal periaqueductal gray results in freezing or flight behavior at low or high intensity, respectively. However, the output structures that mediate these defensive behaviors remain unconfirmed. Here we carried out a targeted classification of neuron types in dorsal periaqueductal gray using multiplex in situ sequencing and then applied cell-type and projection-specific optogenetic stimulation to identify projections from dorsal periaqueductal gray to the cuneiform nucleus that promoted goal-directed flight behavior. These data confirmed that descending outputs from dorsal periaqueductal gray serve as a trigger for directed escape behavior.

scholarly journals Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Mark S Cembrowski ◽  
Lihua Wang ◽  
Ken Sugino ◽  
Brenda C Shields ◽  
Nelson Spruston
Keyword(s):  
Gene Expression ◽  
Granule Cells ◽  
Pyramidal Cells ◽  
Rna Seq ◽  
Mossy Cells ◽  
Neuronal Populations ◽  
Public Resource ◽  
Cell Class ◽  
A Cell

Clarifying gene expression in narrowly defined neuronal populations can provide insight into cellular identity, computation, and functionality. Here, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome characterization of gene expression for the major excitatory neuronal classes of the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical cell classes of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell-class- and region-specific transcriptional description for these populations. This dataset clarifies the transcriptional properties and identities of lesser-known cell classes, and moreover reveals unexpected variation in the trisynaptic loop across the dorsal-ventral axis. We have created a public resource, Hipposeq (http://hipposeq.janelia.org), which provides analysis and visualization of these data and will act as a roadmap relating molecules to cells, circuits, and computation in the hippocampus.

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