Activation of neurons in the ventrolateral periaqueductal grey (vlPAG) matter has been shown to be associated with the expression of freezing responses to conditioned fear (1). These responses are reduced following lesions of the vlPAG, indicating that this structure plays an essential role in the freezing response to conditioned fear (2). Previous anatomical studies have demonstrated pathways from the vlPAG to the cerebellum (3,5). Data are presented here which suggest that such a functional connection, via the inferior olive, plays a role in the expression of conditioned freezing behaviour. Electrical stimulation of the vlPAG in anesthetised male Wistar rats (Sodium Pentobarbital; 60mg.kg-1ip) was found to evoke climbing fibre field potentials in lateral lobule VIII of the cerebellar vermis. The functional significance of this climbing fibre mediated connection was investigated in relation to the finding that chemical stimulation of the vlPAG significantly increases hindlimb-evoked H-reflex amplitude (average increase = 45.2±11%, n=16, P<0.001, Repeated measures ANOVA with Newman-Keuls post-hoc test) in alphaxalone-anesthetised male Wistar rats (Alfaxan; 25mg.kg-1.hr-1iv)*. It was hypothesised that the cerebellum supports this descending effect upon spinal a-motoneurone excitability, which may be linked to the increased muscle tone associated with freezing behaviours. It was found that cerebellectomy (n=4) or neurotoxic lesion (n=4) of the caudal inferior olive abolished the effect of vlPAG stimulation upon H-reflex amplitude. In another set of rats localised lesions of connections to/from vermal lobule VIII, using the toxic tracer cholera toxin b-subunit-saporin (CTb-Sap) (4), were made under ketamine/medetomidine anaesthesia (Vetalar 50mg.kg-1ip and Domitor 300µg.kg-1ip). In these animals (n=12) fear-conditioned freezing was significantly disrupted (P<0.001, Mann-Whitney test) compared to sham controls (n=10), despite appearing otherwise normal in a battery of motor and affective behavioural tasks. The same CTb-Sap treated animals were subsequently alphaxalone-anesthetised (n=6) as previously and the effect of vlPAG stimulation upon H-reflex amplitude found to be abolished. Changes in freezing behaviour as a function of H-reflex facilitation were plotted for individual animals. Consistent with the concept of H-reflex excitability being a proxy measurement for muscle tone underlying freezing behaviour, a positive correlation between the two was found (r2= 0.75, P < 0.05, Linear regression). In summary, these data indicate that vermal lobule VIII of the cerebellum plays an important role in the expression of vlPAG mediated freezing behaviour. (*Preparatory surgery for these experiments was conducted under 1.5-4% halothane anaesthesia.)
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD113
Poster Communications: Functional connections between the ventrolateral periaqueductal grey and cerebellum – a role in fear behaviour?
J. J. Crook1, S. Koutsikou1, E. V. Earl1, J. Leith1, R. Apps1, B. M. Lumb1
1. Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.