Proceedings of The Physiological Society

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, PC255

Poster Communications

Cerebellum: a mediator of fear behaviour

S. Koutsikou1, V. Ahluwalia1, E. Earl1, B. M. Lumb1, R. Apps1

1. Physiology & Pharmacology, University of Bristol, Bristol, United Kingdom.


Cerebellum: a mediator of fear behaviour Stella Koutsikou, Viren Ahluwalia, Emma Earl, Bridget M. Lumb & Richard Apps The ventrolateral sector of the midbrain periaqueductal grey (vlPAG) has a well-established role in conditioned fear (Carrive et al. 1997); characterised by clearly-defined autonomic and sensory changes that are accompanied by freezing behaviour (Carrive 2000). To date, attention has focused on neural pathways underlying autonomic and sensory control from the vlPAG and almost nothing is known about the pathways and mechanisms that link vlPAG to motor control centres. We have previously shown that a neural pathway exists that links the vlPAG with the cerebellar vermal lobule VIII, suggesting that this link may be involved in coordinating behavioural responses associated with vlPAG function (Leith et al. 2009). Here we test the hypothesis that the cerebellum is a key supraspinal structure that links the vlPAG to spinal motor circuits mediating fear-conditioned freezing behaviour. Experiments were carried out in adult male Wistar rats (n=9) and in accordance with the UK Animals (Scientific Procedures) Act 1986. All animals were subjected to a fear conditioning paradigm at least 24hrs prior to either lesion of cerebellar lobule VIII (n=6) using the neurotoxic tracer CTb-Saporin, or sham microinjections (PBS; n=3). All surgical operations were performed under a mixture of ketamine (0.6ml; Vetalar, Pfizer UK) and medetomidine hydrochloride (0.25ml; Domitor, Orion Pharma Finland) mixed in 1ml of 0.9% saline (final anaesthetic dose: 1.8mg.kg-1; i.p.). Lesions of vermal lobule VIII input-output pathways, using CTb-Saporin, significantly disrupted fear-conditioned freezing behaviour (the time animals displayed freezing was reduced by 4929% compared to sham animals, Mann-Whitney, P<0.05). Foot gait analysis and vertical grid test (Seoane et. 2005) were used to assess changes in locomotor activity and muscle tone, respectively. No significant changes in these motor functions were observed in both groups of animals (Wilcoxon matched pairs, P>0.05). However, in the open field test animals treated with CTb-Saporin spent more time in the centre of the open field arena (33.6%) than the Sham animals (17.9%). This is consistent with a reduction in anxiety-like behaviour. Finally, in naïve animals, chemical excitation of vlPAG (with dl-homocysteic acid; 0.05M) exerts a facilitatory effect on the H-reflex, which might reflect the contribution of vlPAG to the tense postures and freezing immobility associated with fear (Koutsikou et al. 2009, 2011). This facilitatory effect is abolished, in alphaxalone-anaesthetised (i.v. Alfaxan, Jurox UK; 25mg.kg-1.hr-1) rats previously injected with CTb-Saporin in cerebellar vermal lobule VIII (n=4, pre-vlPAG vs vlPAG activation; Kruskal-Wallis, P>0.05). Overall, these data provide evidence for a pivotal role for vermal aspects of the olivocerebellar system in linking vlPAG to spinal motor circuits for expression of the affective component of fear behaviour.

Where applicable, experiments conform with Society ethical requirements