Peter M. Lalley

Professor (emeritus)

Contact Information
Email: pmlalley@wisc.edu
(608) 263-4697 Phone
(608) 265-5512 Fax

Research Interests
Neurochemical control of the respiratory network

A network of rhythmically discharging respiratory neurones in the medulla and pons of the brain stem causes the lungs to periodically inflate and deflate, to deliver oxygen to blood and tissue and to expel carbon dioxide. In adult animals the excitability, rhythm and discharge patterns of respiratory neurons are controlled primarily by synaptically released neurotransmitters and neuromodulators.

The focus of research in this laboratory is to identify neurotransmitters, neuromodulators and receptor-activated cellular mechanisms which affect the rhythm and discharge patterns of brain stem respiratory neurons.

The experimental approach involves intra- and extracellular microelectrode recording, and application of receptor-active and second messenger-specific neurochemicals to brain stem respiratory neurons.

Recent studies carried out in vivo have revealed a neuromodulatory mechanism activated by serotonin 5HT-1A receptor agonists that modulates the excitability and rhythm of medullary respiratory neurons [refs. 2,3,5] through actions on intercellular signal parhways [6,8]. Activation of 5HT-1A receptors on brain stem respiratory neurons was found to reverse severe experimentally-induced respiratory disturbances [2,4].

We are also analyzing the sites and cellular mechanisms associated with opioid depression of medullary respiratory neurons, in vivo as well as in vitro. Our objectives in this project are to identify regional sites of opioid depression within the network, related synaptic mechanisms and intracellular transduction pathways.

The ultimate goal is to discover specific neurochemical processes that will prevent respiratory depression without compromising the analgesic effectiveness of opioid drugs.

Selected Publications:

1. Ballanyi, K., Lalley, P.M., Hoch, B. and Richter, D.W. (1997). cAMP-dependent reversal of opioid- and prostaglandin-mediated depression of the isolated respiratory network in newborn rats. J. Physiol. 504, 127-134.
    
2. Lalley, P.M., (1994). The excitability and rhythm of medullary respiratory neurons in the cat are altered by the serotonin receptor agonist 5-methoxy-N,N, dimethyltryptamine. Brain Res. 648, 87-98.
    
3. Lalley, P.M., Benacka, R. Bischoff, A.M. and Richter, D.W. (1997). Nucleus raphe obscurus evokes 5HT-1A receptor-mediated inhibition of respiratory neurons. Brain Res. 747, 156-159.
    
4. Lalley, P.M., Bischoff, A.M. and Richter, D.W. (1994). Serotonin-1A receptor activation suppresses respiratory apneusis in the cat. Neurosci. Lett. 172, 59-62.
    
5. Lalley, P.M., Bischoff, A.M. and Richter, D.W. (1994). 5HT-1A receptor-mediated modulation of medullary expiratory neurones in the cat. J. Physiol. 476, 117-130.
    
6. Lalley, P.M., Pierrefiche, O., Bischoff, A.M. and Richter, D.W. (1997). cAMP-dependent protein kinase modulates expiratory neurons in vivo. J. Neurophysiol. 77, 1119-1131.
    
7. Lalley, P.M., Bischoff, A.M., Schwarzacher, S.W. and Richter, D.W. (1995). 5HT-2 Receptor controlled modulation of medullary respiratory neurones J. Physiol 497, 653-661.
    
8. Richter, D.W., Lalley, P.M., Pierrefiche, O., Haji, A., Bischoff, A.M., Wilken, B. and Hanefeld, F. (1997). Intracellular signal pathways controlling respiratory neurons. Respir. Physiol. 110, 113-123.
    
9. Richter, D.W., Pierrefiche, O., Lalley, P.M., Polder, H.R. (1996). In vivo voltage clamp analysis of neurons within deep layers of the brain. J. Neurosci. Meth. 67, 121-131.

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