Kristen M.S. O'Connell, Ph.D.
Department of Physiology
The University of Tennessee Health Science Center
894 Union Avenue
Memphis, TN 38163
Phone: (901) 448-2648
Lab: 407 Nash Building
Email: Kristen M.S. O'Connell
- Ph.D. Institution: The University of Rochester School of Medicine and Dentistry, Rochester, NY
- Postdoctoral: Colorado State University, Fort Collins, CO
O'Connell Lab Research
Neural pathways regulating food intake and energy balance
Obesity is a significant public health concern in the United States for both adults and children. While weight gain is typically a result of overnutrition, it is increasingly clear that there are physiological changes that occur in the brains of overweight and obese individuals that reinforce this state and make it difficult to lose weight. The research focus in my lab is on the neuronal pathways that control appetite, as we believe these neurons are a particularly important target for understanding how body weight and diet composition influence food intake. We use a variety of techniques, particularly brain slice electrophysiology, multi-photon microscopy, and immunohistochemistry to determine how body weight affects the activity of these neurons and plasticity of the appetite circuit using both normal weight mice and obese mice.
There are three on-going projects in the lab:
- Effects of obesity and diet composition on intrinsic plasticity of orexigenic neurons in the arcuate nucleus of the hypothalamus. There is a well-defined microcircuit between orexigenic and anorexigenic neurons in the arcuate that is critical for the regulation of appetite, hunger and energy expenditure. Thus, the balance of activity of this circuit is an essential element for the maintenance of body weight and is therefore a clinically significant target for weight loss and obesity treatment. In spite of this, the intrinsic electrical properties of these neurons are not well understood. We are therefore exploring the complement of voltage-gated ion channels expressed by these neurons as well as how peripheral signals such as leptin, insulin and ghrelin modulate their activity to influence firing rate in response to an organism's nutritional needs.
- Regulation of olfactory processing by hypothalamic feeding circuits. The smell of pizza or baking bread can often trigger an intense craving for food, even when you are not hungry, suggesting that there is an intimate connection between the olfactory system and the appetite control circuitry of the hypothalamus. We are investigating the hypothesis that the olfactory system plays an important role in regulating energy balance and body weight via a reciprocal circuit with higher brain regions involved in the regulation of food intake as well as the hedonic value of food.
- Influence of maternal diet on the function and development of energy balance circuits in offspring. Although the rapid increase in obesity prevalence almost certainly has no specific monogenetic cause, it is increasingly clear that maternal nutrition and body weight can have a long-lasting impact on body weight homeostasis in offspring that persists into adulthood. In this project, we are investigating the influence that maternal diet and body weight have on the development of hypothalamic energy balance circuits, particularly on the electrophysiological and synaptic properties of these neurons.
- O'Connell KM, Loftus R, Tamkun MM. Localization-dependent activity of the Kv2.1 delayed-rectifier K+ channel. Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12351-6. doi: 10.1073/pnas.1003028107. Epub 2010 Jun 21. PubMed PMID: 20566856; PubMed Central PMCID: PMC2901471.
- O'Connell KM, Whitesell JD, Tamkun MM. Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes. Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H229-37. Epub 2007 Oct 26. PubMed PMID: 17965280.
- Tamkun MM, O'connell KM, Rolig AS. A cytoskeletal-based perimeter fence selectively corrals a sub-population of cell surface Kv2.1 channels. J Cell Sci. 2007 Jul 15;120(Pt 14):2413-23. PubMed PMID: 17606996.
- O'Connell KM, Rolig AS, Whitesell JD, Tamkun MM. Kv2.1 potassium channels are retained within dynamic cell surface microdomains that are defined by a perimeter fence. J Neurosci. 2006 Sep 20;26(38):9609-18. PubMed PMID: 16988031.
- O'Connell KM, Tamkun MM. Targeting of voltage-gated potassium channel isoforms to distinct cell surface microdomains. J Cell Sci. 2005 May 15;118(Pt 10):2155-66. Epub 2005 Apr 26. PubMed PMID: 15855232.
- O'Connell KM, Martens JR, Tamkun MM. Localization of ion channels to lipid Raft domains within the cardiovascular system. Trends Cardiovasc Med. 2004 Feb;14(2):37-42. Review. PubMed PMID: 15030787.