Carrive Research Lab - Brain, Blood Pressure and Stress
Research
Aim and Concepts
The aim of the research conducted in my laboratory is to understand how the brain controls the autonomic and cardiovascular changes associated with stress and emotions.
We are particularly interested in conditioned fear responses. Conditioned fear responses are conditioned emotional responses that occur in anticipation of unpleasant confrontations or events. We have all experienced, for example, the sweaty hands and pounding heart that occur as we are waiting for the mail and bad news is expected or when we face an important meeting for which we are not well prepared. These fear responses are generated in the brain and mediated by a neural network that spans the entire neuraxis, from the forebrain where past experiences are recalled, down to the lower brainstem and spinal cord where autonomic preganglionic neurons are located. We are exploring this network and trying to understand how it is organized, functionally and anatomically.
The outcomes of this research will lead to a better understanding of:
1. The neural substrate of emotions and stress responses,
2. The central regulation of cardiovascular function,
3. The functional/anatomical organization of the limbic forebrain and reticular formation.
Methods
Experiments are conducted in conscious freely moving rats. We use a simple model of conditioned fear called conditioned fear to context. This form of conditioned fear is evoked by re-exposure to a chamber in which small electric footshocks have previously been administered on a few occasions). The fear of receiving more shocks in the box is characterized by a freezing immobility and ultrasonic vocalizations (22 KHz). We have found that it is also associated with a marked and sustained increase in mean arterial blood pressure (+30 mmHg). Our research is about this cardiovascular response and its neural substrate.
- The approach is multi-disciplinary and at the crossroad of animal behavior, cardiovascular physiology and neuroanatomy. Some of the techniques used are:
- Recording of blood pressure, body temperature and activity by radio-telemetry, a new technology that allows continuous recording in conscious, freely moving rats (for more information see http://www.datasci.com).
- Recording of cutaneous temperature using digital infrared thermography.
- Immunohistological detection of Fos, the protein product of the immediate early gene c-fos. Fos is a commonly used marker of neuronal activity. Here it is used to identify the brain regions that are activated during conditioned fear.
- Neuronal tract tracing (retrograde and anterograde) in combination with Fos, to identify the connections between brain regions activated by conditioned fear.
- Intracerebral microinjections of neuronal blockers (e.g., GABA agonists or glutamate antagonists), to verify physiologically the role of brain regions in the cardiovascular response to conditioned fear.
Staff
Dr Daniel ML Vianna (Postdoctoral Fellow)
Leanne Luong (PhD student)
Nick Olsen (PhD student)
Amanda Jellie (Honours student)
Research Grants
Present
2008-2010 NHMRC Research Grant. Central blockade of sympathetic responses to emotional stressors.
P.Carrive
Past
- 2006-2007 NHF Research Grant. Role of Medullary Raphe Nuclei in the cardiovascular response to psychological stress. P. Carrive
- 2006-2008. International Spinal Research Trust. Improving cardiovascular function after spinal cord injury. P. Waite, P. Carrive and A. Mackay-Sim
- 2004-2006 NSW Department of Health. Repair of the injured spinal cord: trialling potential cell therapies. P. Waite, S. Rutkowski, D. Ma, A. Mackay-Sim, B. Tuch, P Carrive, D Tracey, E Burcher, K Ashwell, B Lee, P Siddall, H Alexander, D Brazier, R Millard, H Tao, D Vu.
- 2004 - 2006 NHRMC Project Grant. How the brain suppresses bad memories. F Westbrook, P Carrive, R Richardson.
- 2004 NHRMC Equipment Grant. Infrared thermographic camera. P Carrive, V Macefield, P Waite, T Carroll and S Boutcher.
- 2003-2004 NHF Research Grant. Role of hypothalamic orexin in the cardiovascular response to psychological stress. P Carrive
- 2000-2002 NHMRC Research Grant. Premotor sympathetic control of blood pressure during psychological stress: hypothalamus versus medulla. P Carrive
Publications (from 1999 - present)
Books
Paxinos G., Carrive P, Wang, HQ and Wang PY (1999) A Chemoarchitectonic Atlas of the Rat Brainstem. Academic Press, San Diego. See the cover at
Amazon.com.
Paxinos G., Watson C.; Carrive P, Kirkcaldie, M. and Ashwell K. (2009) Chemoarchitectonic Atlas of the Rat Brain.
Academic Press, San Diego.
Chapters in books
Carrive, P. and Morgan MM (2004). The periaqueductal gray. In: G Paxinos (Ed) The human nervous system (2nd edition), Academic Press, San Diego
Carrive, P. (2009) Aversive Emotions: Emotional Control of the Autonomic Nervous System. In: L. Squire (ed)
Encyclopedia of Neuroscience, Vol 3, pp923-928 Elsevier
Carrive, P. (2009) Central circulatory control: psychological stress (and the defence reaction) In: I.Llewellyn-Smith and A.Verberne (Eds)
Central Regulation of Autonomic Function 2nd Edition. Oxford University Press (in press)
Journal Articles
For copyright reasons reprints can no longer be linked to this web page. However they can be accessed on Pubmed, simply type “carrive” in the search box.
Carrive P, Lee, J and Su, A. (1999) Lidocaine blockade of amygdala output in fear conditioned rats reduces Fos expression in the ventrolateral periaqueductal gray.
Neuroscience, 95: 1071-1080.
Carrive P (2000) Conditioned fear to environmental context: cardiovascular and behavioral components in the rat. Brain Res, 858: 440-445.
Morgan MM and Carrive P (2001) Activation of the Ventrolateral PAG Reduces Locomotion but not Mean Arterial Pressure in Awake, Freely Moving Rats. Neuroscience 102: 905-910.
Dielenberg, RA , Carrive, P
and McGregor, IS (2001) The cardiovascular and behavioral response to cat odor in rats: unconditioned and conditioned effects. Brain Research 897: 228-237.
Carrive, P (2002) Cardiovascular and behavioral components of conditioned fear to context after ganglionic and alpha-adrenergic blockade. Autonomic Neuroscience 98:90-93.
Walker P and Carrive P
(2003) Role of ventrolateral periaqueductal gray neurons in the behavioural and cardiovascular responses to contextual conditioned fear and post-stress recovery. Neuroscience 116: 897-912
Leman, S, Dielenberg RA and Carrive, P (2003) Effect of dorsal priaqueductal gray lesion on cardiovascular and behavioural responses to contextual conditioned fear in rats. Behavioural Brain Research 143: 169-176
Dielenberg RA, Leman, S and Carrive, P (2004) Effect of dorsal priaqueductal gray lesion on cardiovascular and behavioural responses to cat odour exposure in rats. Behavioural Brain Research 153: 487–496
Choi, EA, Leman, S, Vianna D, Waite, PM and Carrive, P (2005) . Expression of cardiovascular and behavioural components of conditioned fear to context in T4 spinally transected rats. Autonomic neuroscience 120: 26-34
Vianna, DML and Carrive, P (2005). Changes in cutaneous and body temperature during and after conditioned fear to context in the rat. European Journal of Neuroscience 21: 2505-2512
McNally G. and Carrive, P. (2006). A telemetric examination of cardiovascular function during the development of and recovery from opiate dependence. Physiology & Behavior 88(1-2):55-60
Carrive, P. (2006). Dual activation of cardiac sympathetic and parasympathetic components during conditioned fear to context in the rat. Clinical and Experimental Pharmacology and Physiology 33:1260-1263.
Florenzano, F., Viscomi, M.T., Mercaldo, V., Longone, P., Bernardi, G., Bagni, C., Molionari, M. and Carrive, P. (2006). P2X2R purinergic receptor subunit mRNA and protein are expressed by all hypothalamic hypocretin/orexin neurons. Journal of Comparative Neurology 498(1): 58-67.
Laird A, Carrive P. and Waite P (2006). Cardiovascular and temperature changes in spinal cord injured rats at rest and during autonomic dysreflexia, J Physiol (Lond) 577, 539-548.
Furlong Y. and Carrive P. (2007). Neurotoxic lesions centered on the perifornical hypothalamus abolish the cardiovascular and behavioural responses of conditioned fear to context but not restraint. Brain Research 1128, 107-109.
Florenzano F, Carrive P, Viscomi M.T., Ferrari F., Latini L., Conversi D., Cabib S., Bagni C. and Molinari M. (2008) Cortical and subcortical distribution of P2X[1]R immunoreative neurons in the rat forebrain. Neuroscience 151(3) 791-801
Laird A., Finch A.M., Waite P.M.E. and Carrive P. (2008) Peripheral changes above and below injury level lead to exaggerated vascular responses following high spinal cord injury. American Journal of Physiology 294(2): H785--792.
Carrive P. and Gorissen M. (2008) Presympathetic neurons of conditioned fear in the rat. European Journal of Neuroscience 28(3): 428-446
Vianna, DML, Allen C. and Carrive P. (2008) Cardiovascular and behavioural responses to conditioned fear after medullary raphe neuronal blockade. Neuroscience 153(4): 1344-1353
Le Bars D. and Carrive P. (2009) Letter to the Editor of Pain about Gemma Ford and David Finn, Clinical correlates of stress-induced analgesia: evidence from pharmacological study. Pain 42(1-2):165-7
Marks A., Vianna DML and Carrive P. (2009) Non-shivering thermogenesis without interscapular brown adipose tissue involvement during conditioned fear in the rat. American Journal of Physiology 96(4):R1239-47.
Laird A., Carrive, P. and Waite, P.M.E. (2009) The effect of treadmill training on autonomic dysreflexia in spinal cord injured rats. Neurorehabilitation and Neural Repair (in press).
Kalincik, T., Jozefcikova, K., Waite, P.M.E. and Carrive P. (2009) Local response to cold in rat tail after spinal cord transection. Journal of Applied Physiology (in press)
Vianna DML and Carrive P. (2009) Inhibition of the cardiovascular response to stress by systemic 5-HT1A activation: sympathoinhibition or anxiolysis? American Journal of Physiology (in press)
Furlong T., Vianna, DML, Liu L and Carrive P. (2009) Hypocretin/orexin contributes to the expression of some but not all forms of stress and arousal. European Journal of Neuroscience (in press)
Kalincik, T., Choi, E.A., Feron, F, Bianco, J, Sutharsan R, Hayward, I, Mackay-Sim, Carrive P. and Waite, P.M.E. (2009) Olfactory ensheathing cells reduce duration of autonomic dysreflexia in rats with high spinal cord injury Autonomic Neuroscience (in press)