Normal heart function depends on complex regulation by the brain, and abnormalities in the brain‒heart axis affect various diseases, such as myocardial infarction and anxiety disorders. However, systematic tracking of the brain regions associated with the input and output of the heart is lacking. In this study, we injected retrograde transsynaptic pseudorabies virus (PRV) and anterograde transsynaptic herpes simplex virus (HSV) into the left ventricular wall of mice to identify the whole-brain regions associated with the input to and output from the heart. We successfully detected PRV and HSV expression in at least 170 brain subregions in both male and female mice. Sex differences were discovered mainly in the hypothalamus and medulla, with male mice exhibiting greater correlation and hierarchical clustering than female mice, indicating reduced similarity and increased modularity of virus expression patterns in male mice. Further graph theory and multiple linear regression analysis of different injection timelines revealed that hub regions of PRV had highly similar clusters, with different brain levels, suggesting a top-down, hierarchically transmitted neural control pattern of the heart. Hub regions of HSV had scattered clusters, with brain regions gathered in the cortex and brainstem, suggesting a bottom-up, leapfrog, multipoint neural sensing pattern of the heart. Both patterns contain many hub brain regions that have been previously overlooked in brain‒heart axis studies. These results provide brain targets for future research and will lead to deeper insight into the brain mechanisms involved in specific heart conditions.
Animals ; Male ; Female ; Heart/physiology* ; Mice ; Herpesvirus 1, Suid ; Brain/physiology* ; Mice, Inbred C57BL ; Brain Mapping ; Efferent Pathways/physiology* ; Afferent Pathways/physiology* ; Simplexvirus ; Sex Characteristics

Descending activation pathways in spinal cord are essential for inducing and modulating autokinesis, but whether the effects of general anesthetic agents on the descending pathways are involved in initiation of skeletal muscle relaxation or not, as well as the underlying mechanisms on excitatory amino acid receptors still remain unclear. In order to explore the mechanisms underlying etomidate's effects on descending activation of spinal cord motoneurons (MNs), the conventional intracellular recording techniques in MNs of spinal cord slices isolated from neonatal rats (7-14 days old) were performed to observe and analyze the actions of etomidate on excitatory postsynaptic potential (EPSP) elicited by electrical stimulation of the ipsilateral ventrolateral funiculus (VLF), which was named VLF-EPSP. Etomidate at 0.3, 3.0 (correspond to clinical concentration) and 30.0 µmol/L were in turn perfused to MN with steadily recorded VLF-EPSPs. At low concentration (0.3 µmol/L), etomidate increased duration, area under curve and/or half-width of VLF-EPSP and N-methyl-D-aspartate (NMDA) receptor-mediated VLF-EPSP component (all P < 0.05), as well as amplitude, area under curve and half-width of non-NMDA receptor-mediated VLF-EPSP component (all P < 0.05), or decreased amplitude and area under curve of VLF-EPSP, its NMDA receptor component, and non-NMDA receptor component (all P < 0.05). However, at 3.0 and 30.0 µmol/L, it was only observed that etomidate exerted inhibitory effects on amplitude and/or duration and/or area under curve of VLF-EPSP (P < 0.05 or P < 0.01) with concentration- and time-dependent properties. Moreover, NMDA receptor-mediated VLF-EPSP component was more sensitive to etomidate at ≥ 3.0 µmol/L than non-NMDA receptor-mediated VLF-EPSP component did. As a conclusion, etomidate, at different concentrations, exerts differential effects on VLF-EPSP and glutamate receptors mediating the synaptic transmission of descending activation of MNs in neonatal rat spinal cord in vitro.
Anesthetics, Intravenous ; pharmacology ; Animals ; Animals, Newborn ; Efferent Pathways ; physiology ; Electric Stimulation ; Etomidate ; pharmacology ; Excitatory Postsynaptic Potentials ; drug effects ; physiology ; Female ; In Vitro Techniques ; Male ; Motor Neurons ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; drug effects ; physiology ; Spinal Cord ; physiology

OBJECTIVE: To investigate the axonal sprouting of somatostatin(SS) positive interneurons in temporal lobe epilepsy. METHODS: 6-8 week-old healthy male SD rats were divided randomly into an epileptic group (treated by lithium and pilocarpine intraperitoneal injection) and a control group (by lithium and normal sodium intraperitoneal injection). Each group was randomly divided into 5 subgroups at 1,7,15,30, amd 60 d after the injection. Immunohistochemistry method was used to detect the number changes of SS or neuronal nuclei (NeuN) positive neurons in different domains of the hippocampus at different time points in each group, and the coexpression of SS positive interneurons combined with NeuN was detected by double immunofluorescence to observe the dynamic changes and axonal sprouting of SS positive interneurons. RESULTS: The number of SS neurons in the experimental group exceeded that in the control group in the CA1 area at 60 d post-status epileptieus SE (P<0.01), and numerous SS positive fibers were seen throughout the layers of the CAl area at 60 d post-SE. NeuN positive neurons in the stratum oriens and stratum radiatum layers in the initiation site of the CA1 area were beyond normal at 60 d post-SE. The number of double labeled SS interneurons gradually rose at 15 d in stratum oriens of CA1, and even exceeded that of the controls in the stratum oriens and stratum radiatum layers of CA1 at 60 d. CONCLUSION The numerous SS positive fibers throughout the layers of the CAl area at 60 d post-SE come from the increased interneurons in the stratum oriens and stratum radiatum layers of CA1 area. The pathological axonal sprouting may play an important role in the generation and compensation of temporal lobe epilepsy.
Animals ; Axons ; metabolism ; pathology ; CA1 Region, Hippocampal ; cytology ; metabolism ; physiopathology ; Efferent Pathways ; pathology ; physiology ; Epilepsy, Temporal Lobe ; chemically induced ; metabolism ; physiopathology ; Interneurons ; cytology ; metabolism ; pathology ; Male ; Pilocarpine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Somatostatin ; metabolism ; Temporal Lobe ; metabolism

OBJECTIVETo investigate the efferent pathway from the dorsal raphe nucleus to the inner ear.

METHODSEleven adult cats weighing 2.0 - 3.0 kg were used. The animals had no middle-ear disease and their auricle reflex was sensitive to sound. They were divided into experimental group (8 cats) and control group (3 cases). The fluorescent tracer cholera toxin subunit-B (CTB) was injected into cat cochlea and the CTB-labelled neurons of dorsal raphe nucleus (DRN) were identified using an immunofluorescence technique after a survival period of 7 days. For studying other fluorescence labelling, the sections containing CTB-labelled neurons were divided into four groups and incubated in antisera directed against tyrosine hydroxylase (TH), serotonin (5-HT), gamma-aminobutyric acid (GABA) and dopamine B-hydroxylase (DBH), respectively. Single-and double-labelled neurons were identified from the DRN.

RESULTS(1) A subpopulation of dorsal raphe nucleus (DRN) neurons were intensely labelled with CTB and these CTB-labelled neurons were densely distributed in a dorsomedial part of the DRN; (2) Four immunolabelling, TH, 5-HT, GABA and DBH were presented throughout the DRN. Of the total population of CTB-labelled neurons, 100% were TH-labelled neurons (double labelling) and no double-stained neuron with 5-HT, GABA and DBH was observed in the DRN.

CONCLUSIONSThere was a projection from DRN to the inner ear and this pathway might be a dopaminergic projection.

Animals ; Cats ; Ear, Inner ; innervation ; metabolism ; Efferent Pathways ; Neurons ; metabolism ; physiology ; Raphe Nuclei ; metabolism ; physiology

The spicoreticulocerebellar (SRC) tract is an indirect spinocerebellar tract formed by the reticular formation (RF), which is connected to the cerebellum and spinal cord. The RF receives ascending fibers to both the spinal enlargement and sends descending fibers to the cerebellum. This study demonstrated that the connectivity of the neurons in the RF is concerned to the cerebellum and spinal cord using the anterograde projection with biotinylated dextran amine (BDA) and retrograde labeling with wheat germ agglutinin-horseradish peroxidase (WGA-HRP). Until now, a preliminary study in mammals has dealt with the afferent and efferent pathways in separating groups of neurons in the RF. There are only few reports on chickens. This study examined the SRC tract in chickens. Following bilateral injections we injected BDA into chicken spinal cord (lumbosacral enlargement) and WGA-HRP into the cerebellum. Both of single- and double-labeled cells were found within the RF. The spinoreticular axons were mainly distributed from the potomedullary junction to the rostral medulla in the rostro-caudally RF levels, for example, nucleus of reticularis (n. r.) pontis oralis, locus coeruleus, n. r. pontis caudalis, n. r. pars gigantocellularis, n. r. gigantocellularis and n. r. parvocellualris. Reticulocerebellar labeling by the WGA- HRP was found in the same place as well as that of the BDA-projection. We observed that the proportion and location of double labeling cells in the chicken were almost similar in each level, comparing to the rodents. These results suggest that the reticular formation is strongly related to the spicoreticulocerebellar tract in chickens.
Afferent Pathways/physiology ; Animals ; Biotin/*analogs&derivatives ; Cerebellum/anatomy&histology/*physiology ; Chickens/*anatomy&histology/*physiology ; Dextrans ; Efferent Pathways/physiology ; Microinjections ; Reticular Formation/anatomy&histology/*physiology ; Spinal Cord/anatomy&histology/*physiology ; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate