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1.
Elife ; 122024 Feb 01.
Article in English | MEDLINE | ID: mdl-38300670

ABSTRACT

Foxb1 -expressing neurons occur in the dorsal premammillary nucleus (PMd) and further rostrally in the parvafox nucleus, a longitudinal cluster of neurons in the lateral hypothalamus of rodents. The descending projection of these Foxb1+ neurons end in the dorsolateral part of the periaqueductal gray (dlPAG). The functional role of the Foxb1+ neuronal subpopulation in the PMd and the parvafox nucleus remains elusive. In this study, the activity of the Foxb1+ neurons and of their terminal endings in the dlPAG in mice was selectively altered by employing chemo- and optogenetic tools. Our results show that in whole-body barometric plethysmography, hM3Dq-mediated, global Foxb1+ neuron excitation activates respiration. Time-resolved optogenetic gain-of-function manipulation of the terminal endings of Foxb1+ neurons in the rostral third of the dlPAG leads to abrupt immobility and bradycardia. Chemogenetic activation of Foxb1+ cell bodies and ChR2-mediated excitation of their axonal endings in the dlPAG led to a phenotypical presentation congruent with a 'freezing-like' situation during innate defensive behavior.


Subject(s)
Bradycardia , Optogenetics , Animals , Mice , Hypothalamus , Neurons , Tachypnea , Forkhead Transcription Factors
2.
Brain Struct Funct ; 227(6): 2049-2072, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35486186

ABSTRACT

The PV2 (Celio 1990), a cluster of parvalbumin-positive neurons located in the ventromedial region of the distal periaqueductal gray (PAG) has not been previously described as its own entity, leading us to study its extent, connections, and gene expression. It is an oval, bilateral, elongated cluster composed of approximately 475 parvalbumin-expressing neurons in a single mouse hemisphere. In its anterior portion it impinges upon the paratrochlear nucleus (Par4) and in its distal portion it is harbored in the posterodorsal raphe nucleus (PDR). It is known to receive inputs from the orbitofrontal cortex and from the parvafox nucleus in the ventrolateral hypothalamus. Using anterograde tracing methods in parvalbumin-Cre mice, the main projections of the PV2 cluster innervate the supraoculomotor periaqueductal gray (Su3) of the PAG, the parvafox nucleus of the lateral hypothalamus, the gemini nuclei of the posterior hypothalamus, the septal regions, and the diagonal band in the forebrain, as well as various nuclei within the reticular formation in the midbrain and brainstem. Within the brainstem, projections were discrete, but involved areas implicated in autonomic control. The PV2 cluster expressed various peptides and receptors, including the receptor for Adcyap1, a peptide secreted by one of its main afferences, namely, the parvafox nucleus. The expression of GAD1 and GAD2 in the region of the PV2, the presence of Vgat-1 in a subpopulation of PV2-neurons as well as the coexistence of GAD67 immunoreactivity with parvalbumin in terminal endings indicates the inhibitory nature of a subpopulation of PV2-neurons. The PV2 cluster may be part of a feedback controlling the activity of the hypothalamic parvafox and the Su3 nuclei in the periaqueductal gray.


Subject(s)
Parvalbumins , Periaqueductal Gray , Animals , Gene Expression , Hypothalamic Area, Lateral/metabolism , Mice , Neurons/metabolism , Parvalbumins/metabolism , Periaqueductal Gray/physiology
3.
Sleep ; 43(11)2020 11 12.
Article in English | MEDLINE | ID: mdl-32343818

ABSTRACT

STUDY OBJECTIVES: The brainstem contains several neuronal populations, heterogeneous in terms of neurotransmitter/neuropeptide content, which are important for controlling various aspects of the rapid eye movement (REM) phase of sleep. Among these populations are the Calbindin (Calb)-immunoreactive NPCalb neurons, located in the Nucleus papilio, within the dorsal paragigantocellular nucleus (DPGi), and recently shown to control eye movement during the REM phase of sleep. METHODS: We performed in-depth data mining of the in situ hybridization data collected at the Allen Brain Atlas, in order to identify potentially interesting genes expressed in this brainstem nucleus. Our attention focused on genes encoding neuropeptides, including Cart (Cocaine and Amphetamine Regulated Transcripts) and Nesfatin 1. RESULTS: While nesfatin 1 appeared ubiquitously expressed in this Calb-positive neuronal population, Cart was coexpressed in only a subset of these glutamatergic NPCalb neurons. Furthermore, an REM sleep deprivation and rebound assay performed with mice revealed that the Cart-positive neuronal population within the DPGi was activated during REM sleep (as measured by c-fos immunoreactivity), suggesting a role of this neuropeptide in regulating some aspects of REM sleep. CONCLUSIONS: The assembled information could afford functional clues to investigators, conducive to further experimental pursuits.


Subject(s)
Nerve Tissue Proteins , Neuropeptides , Animals , Brain Stem/metabolism , Calbindins , Gene Expression , Mice , Nerve Tissue Proteins/genetics , Neurons/metabolism , Neuropeptides/genetics
4.
Soc Cogn Affect Neurosci ; 14(8): 837-847, 2019 08 31.
Article in English | MEDLINE | ID: mdl-31393979

ABSTRACT

In analogy to the appreciation of humor, that of tickling is based upon the re-interpretation of an anticipated emotional situation. Hence, the anticipation of tickling contributes to the final outburst of ticklish laughter. To localize the neuronal substrates of this process, functional magnetic resonance imaging (fMRI) was conducted on 31 healthy volunteers. The state of anticipation was simulated by generating an uncertainty respecting the onset of manual foot tickling. Anticipation was characterized by an augmented fMRI signal in the anterior insula, the hypothalamus, the nucleus accumbens and the ventral tegmental area, as well as by an attenuated one in the internal globus pallidus. Furthermore, anticipatory activity in the anterior insula correlated positively with the degree of laughter that was produced during tickling. These findings are consistent with an encoding of the expected emotional consequences of tickling and suggest that early regulatory mechanisms influence, automatically, the laughter circuitry at the level of affective and sensory processing. Tickling activated not only those regions of the brain that were involved during anticipation, but also the posterior insula, the anterior cingulate cortex and the periaqueductal gray matter. Sequential or combined anticipatory and tickling-related neuronal activities may adjust emotional and sensorimotor pathways in preparation for the impending laughter response.


Subject(s)
Anticipation, Psychological/physiology , Brain/physiology , Laughter/physiology , Laughter/psychology , Sensation/physiology , Adult , Brain Mapping/psychology , Cerebral Cortex/physiology , Emotions/physiology , Female , Gyrus Cinguli/physiology , Humans , Magnetic Resonance Imaging , Male , Young Adult
5.
Brain Struct Funct ; 224(1): 293-314, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30315416

ABSTRACT

Although connections between the orbitofrontal cortex (OFC)-the seat of high cognitive functions-the lateral hypothalamus and the periaqueductal grey (PAG) have been recognized in the past, the precise targets of the descending fibres have not been identified. In the present study, viral tracer-transport experiments revealed neurons of the lateral (LO) and the ventrolateral (VLO) OFC (homologous to part of Area 13 in primates) to project to a circumscribed region in the ventrolateral hypothalamus, namely, the horizontally oriented, cylindrical parvalbumin- and Foxb1-expressing (parvafox) nucleus. The fine collaterals stem from coarse axons in the internal capsule and form excitatory synapses specifically with neurons of the parvafox nucleus, avoiding the rest of the hypothalamus. In its further caudal course, this contingent of LO/VLO-axons projects collaterals to the Su3- and the PV2 nuclei, which lie ventral to the aqueduct in the (PAG), where the terminals fields overlap those deriving from the parvafox nucleus itself. The targeting of the parvafox nucleus by the LO/VLO-projections, and the overlapping of their terminal fields within the PAG, suggest that the two cerebral sites interact closely. An involvement of this LO/VLO-driven circuit in the somatic manifestation of behavioural events is conceivable.


Subject(s)
Hypothalamic Area, Lateral/physiology , Periaqueductal Gray/physiology , Prefrontal Cortex/physiology , Animals , Female , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Genes, Reporter , Hypothalamic Area, Lateral/metabolism , Hypothalamic Area, Lateral/ultrastructure , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Mice, Inbred C57BL , Mice, Transgenic , Neural Pathways/physiology , Neuroanatomical Tract-Tracing Techniques/methods , Parvalbumins/genetics , Parvalbumins/metabolism , Periaqueductal Gray/metabolism , Periaqueductal Gray/ultrastructure , Prefrontal Cortex/metabolism , Prefrontal Cortex/ultrastructure , Rats, Wistar , Recombinant Fusion Proteins/metabolism
6.
Front Behav Neurosci ; 12: 146, 2018.
Article in English | MEDLINE | ID: mdl-30072881

ABSTRACT

The calcium-binding protein parvalbumin (PV) is a recognized marker of short-axon GABA-ergic neurons in the cortex and the hippocampus. However in addition, PV is expressed by excitatory, glutamatergic neurons in various areas of the brain and spinal cord. Depending on the location of these neurons, loading of their synaptic vesicles with glutamate is mediated by either of three vesicular glutamate transporters (VGlut): VGlut1, VGlut2, or VGlut3. Driven by our interest in one of these glutamatergic/PV-expressing cell clusters-the lateral hypothalamic parvafox nucleus-we investigated the functions of this population of neurons by the selective deletion of VGlut2 expression in PV-expressing cells according to the Cre/Lox-approach. PV-Cre;VGlut2-Lox mutant mice are phenotypically characterized by deficits in locomotion and vocalization, by a decreased thermal nociception, and by an increased social dominance. We conducted a search of the Allen Brain Atlas for regions that might co-express the genes encoding PV and VGlut2, and that might thus contribute to the manifestation of the observed phenotypes. Our survey revealed several structures that could contribute to the deficits in locomotion and vocalization, such as the red, the subthalamic and the deep cerebellar nuclei. It also disclosed that a shift in the balance of afferental glutamatergic neurotransmission to the periaqueductal gray matter might be accountable for the decrease in sensitivity to pain and for the increase in social dominance. As a whole, this study broadens the state of knowledge about PV-expressing excitatory neurons.

7.
J Comp Neurol ; 525(15): 3266-3285, 2017 Oct 15.
Article in English | MEDLINE | ID: mdl-28675430

ABSTRACT

Aging-associated ependymal-cell pathologies can manifest as ventricular gliosis, ventricle enlargement, or ventricle stenosis. Ventricle stenosis and fusion of the lateral ventricle (LV) walls is associated with a massive decline of the proliferative capacities of the stem cell niche in the affected subventricular zone (SVZ) in aging mice. We examined the brains of adult C57BL/6 mice and found that ependymal cells located in the adhesions of the medial and lateral walls of the rostral LVs upregulated parvalbumin (PV) and displayed reactive phenotype, similarly to injury-reactive ependymal cells. However, PV+ ependymal cells in the LV-wall adhesions, unlike injury-reactive ones, did not express glial fibrillary acidic protein. S100B+/PV+ ependymal cells found in younger mice diminished in the LV-wall adhesions throughout aging. We found that periventricular PV-immunofluorescence showed positive correlation to the grade of LV stenosis in nonaged mice (<10-month-old), and that the extent of LV-wall adhesions and LV stenosis was significantly lower in mid-aged (>10-month-old) PV-knock out (PV-KO) mice. This suggests an involvement of PV+ ependymal cells in aging-associated ventricle stenosis. Additionally, we observed a time-shift in microglial activation in the LV-wall adhesions between age-grouped PV-KO and wild-type mice, suggesting a delay in microglial activation when PV is absent from ependymal cells. Our findings implicate that compromised ependymal cells of the adhering ependymal layers upregulate PV and display phenotype shift to "reactive" ependymal cells in aging-related ventricle stenosis; moreover, they also contribute to the progression of LV-wall fusion associated with a decline of the affected SVZ-stem cell niche in aged mice.


Subject(s)
Aging/metabolism , Ependyma/metabolism , Lateral Ventricles/metabolism , Parvalbumins/metabolism , Aging/pathology , Animals , Cell Adhesion/physiology , Constriction, Pathologic/metabolism , Constriction, Pathologic/pathology , Ependyma/pathology , Female , Fluorescent Antibody Technique , Forkhead Transcription Factors/genetics , Forkhead Transcription Factors/metabolism , Glial Fibrillary Acidic Protein/metabolism , Gliosis/metabolism , Gliosis/pathology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Lateral Ventricles/pathology , Male , Mice, Inbred C57BL , Mice, Transgenic , Microglia/metabolism , Microglia/pathology , Microscopy, Confocal , Parvalbumins/genetics , S100 Calcium Binding Protein beta Subunit/metabolism
8.
Front Mol Neurosci ; 10: 8, 2017.
Article in English | MEDLINE | ID: mdl-28167900

ABSTRACT

The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with the Allen databases and the murine BrainStars (B*) database. The parvafox nucleus was specifically sampled by laser-capture microdissection and the transcriptome was subjected to a microarray analysis on Affymetrix chips. Eighty-two relevant genes were found to be potentially more expressed in this brain region than in either the cerebral cortex or the hippocampus. When the expression patterns of these genes were counterchecked in the Allen-Database of in-situ hybridizations and in the B*-microarray database, their localization in the parvafox region was confirmed for thirteen. For nine novel genes, which are particularly interesting because of their possible involvement in neuromodulation, the expression was verified by quantitative real time-PCR. Of particular functional importance may be the occurrence of glycine receptors, the presence of which indicates that the activity of the parvafox nucleus is under ascending inhibitory control.

9.
J Comp Neurol ; 524(15): 2955-81, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27292133

ABSTRACT

The parvafox nucleus is an elongated structure that is lodged within the ventrolateral hypothalamus and lies along the optic tract. It comprises axially located parvalbumin (Parv)-positive neurons and a peripheral cuff of Foxb1-expressing ones. In the present study, injections of Cre-dependent adenoviral constructs were targeted to the ventrolateral hypothalamus of Foxb1/Cre mice to label specifically and map the efferent connections of the Foxb1-expressing subpopulation of neurons of the parvafox nucleus. These neurons project more widely than do the Parv-positive ones and implicate a part of the axons known to emanate from the lateral hypothalamus. High labeling densities were found in the dorsolateral and the upper lateral portion of the periaqueductal gray (PAG), the Su3 and PV2 nuclei of the ventrolateral PAG, the cuneiform nucleus, the mesencephalic reticular formation, and the superior colliculus. Intermediate densities of terminals were encountered in the septum, bed nucleus of the stria terminalis, substantia innominata, various thalamic and hypothalamic nuclei, pedunculopontine nucleus, Barrington's nucleus, retrofacial nucleus, and retroambigual nucleus. Scattered terminals were observed in the olfactory bulbs, the prefrontal cortex and the lamina X of the cervical spinal cord. Because the terminals were demonstrated to express the glutamate transporter VGlut2, the projections are presumed to be excitatory. A common denominator of the main target sites of the Foxb1-positive axons of the parvafox nucleus appears to be an involvement in the defensive reactions to life-threatening situations. The hypothalamic parvafox nucleus may contribute to the autonomic manifestations that accompany the expression of emotions. J. Comp. Neurol. 524:2955-2981, 2016. © 2016 Wiley Periodicals, Inc.


Subject(s)
Forkhead Transcription Factors/metabolism , Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/metabolism , Neurons/cytology , Neurons/metabolism , Animals , Behavior, Animal/physiology , Cell Count , Forkhead Transcription Factors/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Immunohistochemistry , Mice, Transgenic , Microscopy, Confocal , Neural Pathways/cytology , Neural Pathways/metabolism , Vesicular Glutamate Transport Protein 2/metabolism
10.
J Comp Neurol ; 524(8): 1529-31, 2016 Jun 01.
Article in English | MEDLINE | ID: mdl-26856681
11.
Brain Res ; 1633: 111-114, 2016 Feb 15.
Article in English | MEDLINE | ID: mdl-26764531

ABSTRACT

The Parvafox-nucleus in the lateral hypothalamus is characterized by the presence of two distinct neural populations, the Parvalbumin (Parv) and the Foxb1-expressing ones. Foxb1-neurons are born at day 10 in the subventricular zone of the mouse mammillary region. It would be interesting to know if the subpopulation of Parv- neurons develop independently at different times and then meet the Foxb1- expressing neurons in the lateral hypothalamus, their final settling place. The aim of this study was to define the period of birth of the Parv-positive neurons using an in-vivo Bromodeoxyuridine-based method in rats. Parv-neurons are generated from embryonic day 10 to day 13, with a peak at day 12. Thus, it appears that the birthdates of the two subpopulations in these two species is similar, perhaps suggesting that they are born from the same neuroepithelial region.


Subject(s)
Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/embryology , Neurogenesis/physiology , Neurons/cytology , Animals , Female , Immunohistochemistry , Male , Parvalbumins/metabolism , Rats , Rats, Wistar
12.
Behav Brain Res ; 298(Pt B): 167-80, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26554726

ABSTRACT

The parvafox nucleus is located ventrolaterally in the lateral hypothalamic area (LHA). Its core and shell are composed of neurons expressing the calcium-binding protein parvalbumin (PV) and the transcription factor Foxb1, respectively. Given the known functions of the LHA and that the parvafox nucleus receives afferents from the lateral orbitofrontal cortex and projects to the periaqueductal gray matter, a functional role of this entity in the expression of positive emotions has been postulated. The purpose of the present study was to ascertain whether the deletion of neurons in the parvafox nucleus influenced the tickling-induced 50-kHz calls, which are thought to reflect positive affective states, in rats. To this end, tickling of the animals (heterospecific play) was combined with intracerebral injections of the excitotoxin kainic acid into the parvafox nucleus. The most pronounced surgery-associated reduction in 50-kHz call-numbers was observed in the group of rats in which, on the basis of PV-immunoreactive-cell counts in the parvafox nucleus, bilateral lesions had been successfully produced. Two other parameters that were implemented to quantify positive affective behaviour, namely, an approach towards and a following of the hand of the tickling experimenter, were likewise most markedly suppressed in the group of rats with bilaterally successful lesions. Furthermore, positive correlations were found between each of the investigated parameters. Our data afford evidence that the parvafox nucleus plays a role in the production of 50-kHz calls in rats, and, more generally, in the expression of positive emotions.


Subject(s)
Affect/physiology , Choice Behavior/physiology , Hypothalamic Area, Lateral/physiology , Social Behavior , Touch Perception/physiology , Vocalization, Animal/physiology , Animals , Cell Count , Cohort Studies , Female , Hypothalamic Area, Lateral/physiopathology , Kainic Acid , Male , Microglia/physiology , Motor Activity/physiology , Parvalbumins/metabolism , Rats, Wistar , Ultrasonics
13.
J Comp Neurol ; 524(8): 1608-15, 2016 Jun 01.
Article in English | MEDLINE | ID: mdl-26287648

ABSTRACT

The insular cortex is fundamentally involved in the processing of interoceptive information. It has been postulated that the integrative monitoring of the bodily responses to environmental stimuli is crucial for the recognition and experience of emotions. Because emotional arousal is known to be closely coupled to functions of the anterior insula, we suspected laughter to be associated primarily with neuronal activity in this region. An anatomically constrained re-analysis of our imaging data pertaining to ticklish laughter, to inhibited ticklish laughter, and to voluntary laughter revealed regional differences in the levels of neuronal activity in the posterior and mid-/anterior portions of the insula. Ticklish laughter was associated specifically with right ventral anterior insular activity, which was not detected under the other two conditions. Hence, apparently, only laughter that is evoked as an emotional response bears the signature of autonomic arousal in the insular cortex.


Subject(s)
Cerebral Cortex/physiology , Laughter/physiology , Humans
14.
J Comp Neurol ; 524(8): 1616-23, 2016 Jun 01.
Article in English | MEDLINE | ID: mdl-26179507

ABSTRACT

The lateral hypothalamus has been long suspected of triggering the expression of positive emotions, because stimulations of its tuberal portion provoke bursts of laughter. Electrophysiological studies in various species have indeed confirmed that the lateral hypothalamus contributes to reward mechanisms. However, only the rudiments of the neural circuit underlying the expression of positive emotions are known. The prefrontal cortex, the lateral hypothalamus, and the periaqueductal gray matter (PAG) are involved in these circuits; so, too, are the brainstem nuclei that control the laryngeal muscles and subserve mimicry, as well as the cardiovascular and respiratory systems. The implicated populations of hypothalamic neurons have not been defined either anatomically or molecularly. One promising candidate is the novel parvafox nucleus, which we recently described, in the murine medial forebrain bundle (mfb), which specifically expresses parvalbumin and Foxb1. With the molecularly defined parvafox nucleus as a centerpiece, the inputs from the prefrontal cortex and the projections to the PAG and brainstem can be studied with precision. By drawing on genetic approaches, it will be possible to manipulate the circuitry selectively with spatial and temporal exactitude and to evaluate the concomitant autonomic changes. These data will serve as a basis for imaging studies in humans using various paradigms to provoke the expression of positive emotions. In conclusion, studies of the hypothalamic parvafox nucleus will reveal whether this entity represents the fulcrum for positive emotions, as is the amygdala for fear and the insula for disgust.


Subject(s)
Emotions/physiology , Hypothalamic Area, Lateral/physiology , Medial Forebrain Bundle/physiology , Animals , Humans
15.
Glia ; 63(4): 567-94, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25421913

ABSTRACT

The calcium-binding protein parvalbumin (PV) hallmarks subpopulations of interneurons in the murine brain. We serendipitously observed the de novo expression of PV in ependymal cells of the lateral ventricle wall following in vivo lesioning and brain slicing for the preparation of organotypic hippocampal slice cultures (OHSCs). In OHSCs, de novo PV-expression begins shortly after the onset of culturing, and the number of ependymal cells implicated in this process increases with time. PV-immunopositive ependymal cells aggregate and form compact cell clusters, which are characterized by lumen-formation and beating cilia. Scratches inflicted on such clusters with a sharp knife are rapidly closed. Exposure of OHSCs to NF-КB-inhibitors and to antioxidants reduces PV-expression in ependymal cells, thereby implicating injury-induced inflammation in this process. Indeed, in vivo stab injury enhances PV-expression in ependymal cells adjacent to the lesion, whereas neuraminidase denudation is without effect. PV-knock-out mice manifest an impaired wound-healing response to in vivo injury, and a reduced scratch-wound reparation capacity in OHSCs. Whole-transcriptome analysis of ependymal-cell clusters in OHSCs revealed down-regulation of genes involved in cytoskeletal rearrangement, cell motility and cell adhesion in PV-knock out mice as compared with wild-type mice. Our data indicate that the injury-triggered up-regulation of PV-expression is mediated by inflammatory cytokines, and promotes the motility and adhesion of ependymal cells, thereby contributing to leakage closure by the re-establishment of a continuous ependymal layer.


Subject(s)
Brain Injuries/metabolism , Brain Injuries/pathology , Ependyma/cytology , Parvalbumins/genetics , Wound Healing , Animals , Cell Adhesion/genetics , Cell Culture Techniques , Cell Movement/genetics , Cytokines/blood , Down-Regulation , Ependyma/metabolism , Inflammation/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Parvalbumins/deficiency , Up-Regulation
16.
Neurosci Lett ; 566: 111-4, 2014 Apr 30.
Article in English | MEDLINE | ID: mdl-24576653

ABSTRACT

In the ventrolateral hypothalamus, the PV1-nucleus is defined by its population of parvalbumin-expressing neurons. During embryogenesis, the ventrolateral hypothalamus is colonized also by Foxb1-expressing neurons. In adult Foxb1-EGFP mice, many immunofluorescent neurons were found within the region that is occupied by the PV1-nucleus. They formed a cloud around the axial cord of the parvalbumin-immunopositive cells, which they greatly outnumber (3:1). Only a small proportion of the neurons in the PV1-nucleus co-expressed both parvalbumin and Foxb1. In the light of these findings, a redesignation of this lateral hypothalamic structure as the PV1-Foxb1 nucleus would more accurately reflect its specific biochemical properties.


Subject(s)
Forkhead Transcription Factors/metabolism , Hypothalamic Area, Lateral/metabolism , Neurons/metabolism , Parvalbumins/metabolism , Animals , Forkhead Transcription Factors/genetics , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Mice, Transgenic , Parvalbumins/genetics
17.
J Comp Neurol ; 521(14): 3133-53, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-23787784

ABSTRACT

A solitary cluster of parvalbumin-positive neurons--the PV1 nucleus--has been observed in the lateral hypothalamus of rodents. In the present study, we mapped the efferent connections of the PV1 nucleus using nonspecific antero- and retrograde tracers in rats, and chemoselective, Cre-dependent viral constructs in parvalbumin-Cre mice. In both species, the PV1 nucleus was found to project mainly to the periaqueductal grey matter (PAG), predominantly ipsilaterally. Indirectly in rats and directly in mice, a discrete, longitudinally oriented cylindrical column of terminal fields (PV1-CTF) was identified ventrolateral to the aqueduct on the edge of the PAG. The PV1-CTF is particularly dense in the rostral portion, which is located in the supraoculomotor nucleus (Su3). It is spatially interrupted over a short stretch at the level of the trochlear nucleus and abuts caudally on a second parvalbumin-positive (PV2) nucleus. The rostral and the caudal portions of the PV1-CTF consist of axonal endings, which stem from neurons scattered throughout the PV1 nucleus. Topographically, the longitudinal orientation of the PV1-CTF accords with that of the likewise longitudinally oriented functional modules of the PAG, but overlaps none of them. Minor terminal fields were identified in a crescentic column of the lateral PAG, as well as in the Edinger-Westphal, the lateral habenular, and the laterodorsal tegmental nuclei. So far, no obvious functions have been attributed to this small, circumscribed column ventrolateral to the aqueduct, the prime target of the PV1 nucleus.


Subject(s)
Hypothalamus/cytology , Neural Pathways/physiology , Neurons/metabolism , Parvalbumins/metabolism , Adenoviridae , Animals , Biotin/analogs & derivatives , Biotin/metabolism , Brain Mapping , Channelrhodopsins , Dextrans/metabolism , Female , Functional Laterality , Green Fluorescent Proteins/genetics , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Male , Mice , Mice, Transgenic , Parvalbumins/genetics , Periaqueductal Gray/cytology , Periaqueductal Gray/metabolism , Rats , Rats, Wistar , Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate/metabolism , Red Fluorescent Protein
18.
Cereb Cortex ; 23(6): 1280-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-22508768

ABSTRACT

The burst of laughter that is evoked by tickling is a primitive form of vocalization. It evolves during an early phase of postnatal life and appears to be independent of higher cortical circuits. Clinicopathological observations have led to suspicions that the hypothalamus is directly involved in the production of laughter. In this functional magnetic resonance imaging investigation, healthy participants were 1) tickled on the sole of the right foot with permission to laugh, 2) tickled but asked to stifle laughter, and 3) requested to laugh voluntarily. Tickling that was accompanied by involuntary laughter activated regions in the lateral hypothalamus, parietal operculum, amygdala, and right cerebellum to a consistently greater degree than did the 2 other conditions. Activation of the periaqueductal gray matter was observed during voluntary and involuntary laughter but not when laughter was inhibited. The present findings indicate that hypothalamic activity plays a crucial role in evoking ticklish laughter in healthy individuals. The hypothalamus promotes innate behavioral reactions to stimuli and sends projections to the periaqueductal gray matter, which is itself an important integrative center for the control of vocalization. A comparison of our findings with published data relating to humorous laughter revealed the involvement of a common set of subcortical centers.


Subject(s)
Brain Mapping , Brain/blood supply , Laughter/physiology , Magnetic Resonance Imaging , Adult , Brain/physiology , Female , Foot/innervation , Functional Laterality , Humans , Image Processing, Computer-Assisted , Inhibition, Psychological , Linear Models , Male , Oxygen/blood , Physical Stimulation , Voice , Young Adult
19.
J Comp Neurol ; 520(4): 798-815, 2012 Mar 01.
Article in English | MEDLINE | ID: mdl-22020694

ABSTRACT

In the lateral hypothalamus, groups of functionally related cells tend to be widely scattered rather than confined to discrete, anatomically distinct units. However, by using parvalbumin (PV)-specific antibodies, a solitary, compact cord of PV-immunoreactive cells (the PV1-nucleus) has been identified in the ventrolateral tuberal hypothalamus in various species. Here we describe the topography, the chemo-, cyto-, and myeloarchitectonics, and the ultrastructure of this PV1-nucleus in rodents. The PV1-nucleus is located within the ventrolateral division of the medial forebrain bundle. In the horizontal plane, it has a length of 1 mm in mice and 2 mm in rats. PV-immunoreactive perikarya fall into two distinct size categories and number (~800 in rats and ~400 in mice). They are intermingled with PV-negative neurons and coarse axons of the medial forebrain bundle, some of which are PV-positive. Symmetric and asymmetric synapses, as well as PV-positive and PV-negative fiber endings, terminate on the perikarya of both PV-positive and PV-negative neurons. PV-positive neurons of the PV1-nucleus express glutamate, not γ-aminobutyric acid (GABA), the neurotransmitter that is usually associated with PV-containing nerve cells. Although we could not find evidence that PV1 neurons express either catecholamines or known neuropeptides, they sometimes are interspersed with the fibers and terminals of such cells. From its analogous topographical situation, the PV1-nucleus could correspond to the lateral tuberal nucleus in humans. We anticipate that the presence of the marker protein PV in the PV1-nucleus of the rodent hypothalamus will facilitate future studies relating to the connectivity, transcriptomics, and function of this entity.


Subject(s)
Hypothalamic Area, Lateral/anatomy & histology , Parvalbumins/metabolism , Animals , Antibodies/analysis , Calbindin 2 , Calbindins , Cell Count , Cerebrovascular Circulation/physiology , Female , Glutamate Decarboxylase/metabolism , Glutamic Acid/metabolism , Hypothalamic Area, Lateral/cytology , Hypothalamic Area, Lateral/ultrastructure , Immunohistochemistry , Intracellular Signaling Peptides and Proteins/metabolism , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Microscopy, Electron , Neurons/ultrastructure , Neuropeptides/metabolism , Orexins , Plant Lectins , Rats , Rats, Wistar , Receptors, N-Acetylglucosamine , S100 Calcium Binding Protein G/metabolism , gamma-Aminobutyric Acid/metabolism
20.
J Neuropathol Exp Neurol ; 69(3): 281-93, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20142762

ABSTRACT

Muscle weakness in Charcot-Marie-Tooth Type 1A disease (CMT1A) caused by mutations in peripheral myelin protein 22 (PMP22) has been attributed to an axonopathy that results in denervation and muscle atrophy. The underlying pathophysiological mechanisms involved are not understood. We investigated motor performance, neuromuscular junctions (NMJs), physiological parameters, and muscle morphometry of PMP22 transgenic mice. Neuromuscular junctions were progressively lost in hindlimb muscles of PMP22 transgenic mice, but their motor performance did not completely deteriorate during the observation period. There was considerable variability, including in laterality, in deficits among the animals. Cross-sectional areas and mean fiber size measurements indicated variable myofiber atrophy in hindlimb muscles. There was substantial concomitant axonal sprouting, and loss of neuromuscular junctions was inversely correlated with the accumulated length of axonal branches. Synaptic transmission studied in isolated nerve/muscle preparations indicated variable partial muscle denervation. Acetylcholine sensitivity was higher in the mutant muscles, and maximum tetanic force evoked by direct or indirect stimulation, specific force, and wet weights were markedly reduced in some mutant muscles. In summary, there is partial muscle denervation, and axons may retain some regenerative capacity but fail to reinnervate muscles in PMP22 transgenic mice.


Subject(s)
Charcot-Marie-Tooth Disease/pathology , Charcot-Marie-Tooth Disease/physiopathology , Growth Cones/physiology , Motor Neurons/physiology , Neuromuscular Junction/pathology , Neuromuscular Junction/physiopathology , Acetylcholine/metabolism , Animals , Charcot-Marie-Tooth Disease/genetics , Disease Models, Animal , Disease Progression , Female , Growth Cones/ultrastructure , Hindlimb/innervation , Hindlimb/physiopathology , Male , Mice , Mice, Transgenic , Motor Neurons/cytology , Muscle Contraction/genetics , Muscle Weakness/genetics , Muscle Weakness/pathology , Muscle Weakness/physiopathology , Muscular Atrophy/genetics , Muscular Atrophy/pathology , Muscular Atrophy/physiopathology , Nerve Regeneration/genetics , Neuronal Plasticity/genetics , Peripheral Nerves/pathology , Peripheral Nerves/physiopathology , Synaptic Transmission/genetics
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