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

• Published in: Behavioural brain research Vol. 319; pp. 135 - 147
• Main Authors: Ullah, Farhad, dos Anjos-Garcia, Tayllon, Mendes-Gomes, Joyce, Elias-Filho, Daoud Hibrahim, Falconi-Sobrinho, Luiz Luciano, Freitas, Renato Leonardo de, Khan, Asmat Ullah, Oliveira, Ricardo de, Coimbra, Norberto Cysne
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-02-2017
• Subjects: Analysis of Variance; Animals; Biotin - analogs & derivatives; Biotin - metabolism; Biotinylated dextran amine anterograde neurotracer; Cobalt - pharmacology; Dextrans - metabolism; Dorsomedial part of ventromedial hypothalamus; Escape Reaction - drug effects; Escape Reaction - physiology; Excitatory Amino Acid Agonists - pharmacology; Fos protein; Freezing Reaction, Cataleptic - drug effects; Glutamic acid/aspartic acid system; Male; N-Methylaspartate - pharmacology; Neural Pathways - drug effects; Neural Pathways - physiology; Oncogene Proteins v-fos - metabolism; Panic - physiology; Panic-like behaviour; Periaqueductal Gray - drug effects; Periaqueductal Gray - physiology; Periaqueductal grey matter; Rats; Rats, Wistar; Ventromedial Hypothalamic Nucleus - drug effects; Ventromedial Hypothalamic Nucleus - physiology; Dorsomedial part of ventromedial hypothalamus; Fos protein; Panic-like behaviour; Biotinylated dextran amine anterograde neurotracer; Glutamic acid/aspartic acid system; Periaqueductal grey matter
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2016.11.026

The chemical stimulation of the dorsomedial division of the ventromedial hypothalamic nucleus (dmVMH) with NMDA at 9nmol elicits panic-like behavioural responses with increase of Fos protein in neuronal nuclei of the dorsal periaqueductal grey matter (dPAG). Fos-immunolabelled neurons in dPAG are surrounded by dmVMH-dPAG neuronal pathways terminal buttons. The inactivation of synaptic contacts in dPAG with CoCl2 abolishes the panic-like behaviour elicited by dmVMH neuronal activation with 9nmol of NMDA.
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•dmVMH neurons can trigger panic-like escape but does not act independently.•dPAG neurons mainly produce freezing and explosive escape independently.•Projections from dmVMH to dPAG play an important role in the elaboration of defence.
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 CoCl2 was 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.