Research Summary

Our laboratory consists of systems neuroscientists who try to unravel the complexities of the billions of cells that comprise the mammalian brain. Our laboratory investigates the organization of brain and the behaviors it produces by describing the neuroanatomy of a region and then testing its cardiovascular, respiratory, locomotor and neurophysiological function. We have emphasized the reflex circuits in the brainstems of mammals in the past, specifically somatovisceral interactions, where a stimulus to the body’s surface elicits changes in cardiovascular and respiratory behavior. More recently, we have shifted our focus to translation research, attempting to integrate conceptual basic science towards human application. We now investigate a disease disrupting motor function, Parkinson disease, as well as defining a new pathway which may be important for chronic deep pain.

The Etiology of Parkinson Disease
Parkinson disease (PD) is the most common neurodegenerative movement disorder, affecting 2% of individuals over age 65 and 4-5% over 85 years. PD is characterized by bradykinesia, tremor at rest, rigidity and postural rigidity; by the loss of dopaminergic neurons in the substantia nigra (SN); and the accumulation of the protein alpha-synuclein (a-syn) as Lewy bodies and Lewy neurites in the remaining neurons. Although numerous theories have been postulated to explain the death of dopaminergic neurons in the SN, the etiology of PD presently is still unknown. My colleagues and I wish to prove the ‘catecholaldehyde hypothesis’, which proposes that a toxic metabolite of dopamine breakdown, 3,4-dihydroxyphenylacetaldehyde (DOPAL), accumulates in dopamine neurons and eventually kills them. We have shown already DOPAL induces formation of α-syn in neurons and kills them in vitro (Burke et al., 2008), that DOPAL also kills neurons in vivo, and induces a motor behavior indicative of dopamine depletion (Panneton et al., 2010). We are now exploring mechanisms by which DOPAL may increase in DA neurons to induce their death.

The Caudal Pressor Area.
The caudal pressor area, or CPA, includes neurons in the caudalmost ventrolateral medulla which induce an increase in arterial blood pressure when stimulated. Neurons in this area have been implicated both in regulating arterial pressure as well as important in pain. We have defined the functional limits of the CPA (Sun & Panneton, 2002) and described its brainstem connections to neurons implicated both in cardiovascular function and in responses to noxious stimulation (Sun & Panneton, 2005). The CPA has been implicated in the blood pressure changes seen in exercise (the exercise pressor response; see Panneton et al., 2005), and may be important for changes in heart rate and respiration (Sun & Panneton, 2001), but not the increase in blood pressure after nasal stimulation (Panneton et al., 2008). Neurons in a similar area of the caudalmost ventrolateral medulla receive robust projections from the superficial medullary dorsal horn and are activated by injecting algesics into the temporalis muscle (Panneton et al., 2011). We propose the caudalmost ventrolateral medulla (CPA) is the rostral part of a spinal system important in chronic deep pain.

The Mammalian Diving Response.

The diving response, best seen in aquatic mammals, is the most powerful autonomic response known. It is a complex of reflexes that generate the behaviors of apnea (an inhibition of respiration), a bradycardia (a slowing of heart rate), and a massive peripheral vasoconstriction (the narrowing of blood vessels), apparently in response to a somatic stimulus. It serves the organism by preserving intrinsic oxygen stores for the most important organs. We train rats to dive underwater while recording their blood pressure and heart rate (see appended movie). These responses are similar to those induced in anesthetized animals by stimulating their nasal mucosa with vapors of ammonia or carbon dioxide, water, or electrically. Physiological experiments monitoring neural, cardiovascular, and respiratory parameters are combined with neuroanatomical studies to elucidate the brainstem circuit for the powerful diving response.

The anterior ethmoidal nerve (Panneton, 1991; Panneton et al., 2006) innervates the anterior nasal mucosa and induces responses similar to those of the diving response when stimulated (McCulloch & Panneton, 1997 & 1999). This nerve terminates in ventral parts of the trigeminal medullary dorsal horn (MDH) (Panneton, 1991; Panneton et al., 2006), an area important for mediating the diving response (Panneton & Yavari, 1995). Trigeminal neurons in similar areas of the MDH project to brainstem autonomic nuclei (Panneton et al., 1994; Panneton et al., 2000; Panneton et al., 2006). It is probable that the sympathetically mediated vasoconstriction is mediated by neurons in the rostroventrolateral medulla (McCulloch et al., 1999) while cardiac motoneurons in the caudal medulla mediate the bradycardia (Panneton et al., 1996). Why the apnea is induced is unknown, but may be due to trigeminal projections to the ventral medulla, where central respiratory chemoreceptors are found (Panneton et al., 2010). We know circuits for these reflex responses are maintained in the brainstem and spinal cord (Panneton et al., 2012a) and that the cardiovascular responses use neurons different from those of swimming behavior Panneton et al., 2012b). We are finalizing our work on this remarkable response, but wish still to implicate the diving response as the cause of the Sudden Infant Death Syndrome (SIDS) (Yavari et al., 1996), where the infant fails to breathe and dies without cause.

To view a sample video of our rat swimming select either the quicktime mov file or the avi windowsmedia file. Each contains the same video footage.

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Download Quicktime Here || Download Media Player Here

Dr. Panneton in the previous 31 years has received funds from the National Institutes of Health (7 awards), VA Merit Award (1 award), Missouri Heart Association (1 award), Saint Louis University Medical School (4 awards), and TEVA Pharmaceutical Corp (2 awards).

Professional Experience

• 1978-1981, Postdoctoral Fellow Department of Anatomy and Neurobiology Washington University School of Medicine
• 1981-2004, Assistant, Associate, and Professor of Anatomy and Neurobiology Saint Louis University School of Medicine
• 2004 – present, Professor of Pharmacological and Physiological Science Saint Louis University School of Medicine

Professional Memberships

• Society for Neuroscience
• American Physiological Society
• American Association of Anatomists
• IBRO
• American Academy of Neurology

Publications

Selected Scholarly Publications

The Etiology of Parkinson Disease

Burke, W.J., V.B. Kumar, W.M. Panneton, Q. Gan, N. Pandey, M.W. Franko, M. O’Dell, S.W. Li, Y. Pan, H.D. Chung and J.E. Galvin: Aggregation of a-synuclein aggregation by DOPAL, the monoamine oxidase metabolite of dopamine.  Acta Neuropath. 115:193-203, 2008. PMID: 17965867

Panneton, W.M., V.B. Kumar, Q. Gan, W.J. Burke and J.E. Galvin: The neurotoxicity of DOPAL: Behavioral and stereological data with implications for Parkinson disease. PLoS ONE 5: e15251, 2010.

The Caudal Pressor Area

Sun, W. and W.M. Panneton: Negative chronotropism of the heart is inhibited with lesions of the caudal medulla in the rat. Brain Res., 908:208-212, 2001. PMID: 11454332

Sun, W. and W.M. Panneton: Defining projections from the caudal pressor area of the caudal ventrolateral medulla. J. Comp. Neurol. 482:273-293, 2005. PMID: 15690490

Panneton, W.M., Q. Gan and R. Juric: The central termination of sensory fibers from nerves to the gastrocnemius muscle of the rat.  Neuroscience 134:175-187, 2005. PMID: 15953682

Panneton, W.M., W. Sun, and Q. Gan: Pressor responses to nasal stimulation are unaltered after disrupting the CPA.  Autonomic Neuroscience: Basic and Clinical 144:13-21, 2008.  PMID: 18809361

Panneton, W.M., Gan, Q. and Livergood, R.: A trigeminoreticular pathway: Implications in pain.  PloS ONE 10.1371/journal.pone.0024499, 2011. PMID: 21957454

The Mammalian Diving Response

Panneton, W.M.: Trigeminal mediation of the diving response in the muskrat. Brain Res. 560:321-325, 1991. PMID: 1760738

Panneton, W.M., S.N. Johnson and N.D. Christensen: Trigeminal projections to the peribrachial region in the muskrat. Neuroscience 58:605-625, 1994. PMID: 7513388

Panneton, W.M., and P. Yavari:  A medullary dorsal horn relay for the diving response in the muskrat, Ondatra zibethicus: evidence for excitatory amino acid transmission.  Brain Res., 691:37-45, 1995. PMID: 8590063

Yavari, P., P.F. McCulloch and W.M. Panneton: Trigeminally-mediated alteration of cardiorespiratory rhythms during transnasal application of carbon dioxide in the rat.  J. Auto. Nerv. Syst. 61:195-200, 1996. PMID: 8946342

Panneton, W.M., P.F. McCulloch, Y. Tan, Y. Tan and P. Yavari: Brainstem origin of preganglionic motoneurons in the muskrat.  Brain Res., 738:342-346, 1996. PMID: 8955533

McCulloch, P.F. and W.M. Panneton: FOS immunohistochemical determination of brainstem neuronal activation in the muskrat after nasal stimulation. Neuroscience, 78:913-925, 1997. PMID: 9153669

McCulloch, P.F, K.M. Faber and W.M. Panneton: Electrical stimulation of small diameter fibers within the anterior ethmoidal nerve produces the diving response.  Brain Res., 830:24-32, 1999. PMID: 10350556

McCulloch, P.F., W.M. Panneton and P.G. Guyenet: The RVLM mediates sympathetic activation produced by chemical activation of the nasal mucosa.  J. Physiol. (Lond.), 516:471-484, 1999. PMID: 10087346

Panneton, W.M., P.F. McCulloch and W. Sun: Trigemino-autonomic connections in the muskrat:  the neural substrate for the diving response.  Brain Res., 874:48-65, 2000. PMID: 10936223

McCulloch, P.F. and W.M. Panneton: Activation of brainstem catecholaminergic neurons during voluntary diving in rats. Brain Res. 984:42-53, 2003. PMID: 12932838

Panneton, W.M., Q. Gan and R. Juric:  Brainstem projections from recipient zones of the anterior ethmoidal nerve in the medullary dorsal horn. Neuroscience 141:889-906, 2006.  PMID: 16753263

Panneton, W.M., Q. Gan, and R. Juric: The rat: a laboratory model for studies of the diving response.  J. Appl. Physiol. 108: 811-820, 2010. PMID: 20093670

Panneton, W.M., Q. Gan, and T.E. Dahms: Cardiorespiratory and neural consequences of rats brought past their aerobic dive limit.  J. Appl. Physiol. 109:1256-1269, 2010. PMID: 20705947

Panneton, W.M., Gan, Q. and Sun, D.W.: Persistence of the nasotrigeminal reflex after pontomedullary transection.  Resp. Physiol. & Neurobiol. 180:230-236, 2012a. PMID: 22154693

Panneton, W.M., Q. Gan, and R. Juric: Activation of brainstem neurons by underwater diving. Front Physiol. 3:111, doi:10:3389/fphys.2012.00111, 2012b. PMID: 22563319

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