title: Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.
abstract: The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours.
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Department of Animal Sciences, Quaid-i-Azam University, 45320 Islamabad, Pakistan.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil.
authors.forename: Tayllon
authors.initials: T
authors.lastname: Dos Anjos-Garcia
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220, São Paulo, Brazil.
authors.forename: Joyce
authors.initials: J
authors.lastname: Mendes-Gomes
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil.
authors.forename: Daoud Hibrahim
authors.initials: DH
authors.lastname: Elias-Filho
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil.
authors.forename: Luiz Luciano
authors.initials: LL
authors.lastname: Falconi-Sobrinho
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Multiuser Centre of Neurophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil; Laboratory of Pain and Emotions, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil.
authors.forename: Renato Leonardo de
authors.initials: RL
authors.lastname: Freitas
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Department of Eastern Medicine and Surgery, School of Medical and Health Sciences of the University of Poonch Rawalakot, Azad Jammu and Kashmir, Pakistan.
authors.forename: Asmat Ullah
authors.initials: AU
authors.lastname: Khan
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220, São Paulo, Brazil; Mato Grosso Federal University Medical School, Industrial Sector, Sinop, 78550-000, Mato Grosso, Brazil.
authors.forename: Ricardo de
authors.initials: R
authors.lastname: Oliveira
authors.affiliation: Laboratory of Neuroanatomy & Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; NAP-USP-Neurobiology of Emotions Research Centre (NuPNE), Ribeirão Preto Medical School of the University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, 14049-900, São Paulo, Brazil; Multiuser Centre of Neurophysiology, Department of Surgery and Anatomy, Ribeirão Preto Medical School of the University of São Paulo (USP), Av. Bandeirantes, 3900, 14049-900, Ribeirão Preto, São Paulo, Brazil; Behavioural Neurosciences Institute (INeC), Av. do Café, 2450, Monte Alegre, Ribeirão Preto, 14050-220, São Paulo, Brazil. Electronic address: nccoimbr@fmrp.usp.br.
authors.forename: Norberto Cysne
authors.initials: NC
authors.lastname: Coimbra
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D003035:Cobalt / Q000494:pharmacology; D003911:Dextrans / Q000378:metabolism; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010200:Panic / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*
chemical_list: D003911:Dextrans; D018690:Excitatory Amino Acid Agonists; D016761:Oncogene Proteins v-fos; C076397:biotinylated dextran amine; D003035:Cobalt; D016202:N-Methylaspartate; D001710:Biotin; C018021:cobaltous chloride
keywords: Biotinylated dextran amine anterograde neurotracer; Dorsomedial part of ventromedial hypothalamus; Fos protein; Glutamic acid/aspartic acid system; Panic-like behaviour; Periaqueductal grey matter