Dr. Heinricher's laboratory investigates brainstem mechanisms involved in pain modulation. Their focus is on opioid-sensitive circuits within the rostral ventral medulla (RVM), which is a crucial element in a pain-modulating network with links in the midbrain, medulla and spinal cord. This network contributes to the variability in pain sensitivity seen in different situations (for example under conditions of fear or extreme stress), and it is an important substrate for opioids and other analgesic drugs such as cannabinoids. The laboratory uses single cell recording in combination with pharmacological tools to analyze how this system is activated, and they have identified two distinct classes of pain modulating neurons.
- ON cells are directly sensitive to opioids, and they recently showed that these neurons facilitate nociceptive transmission.
- OFF-cells exert a net inhibitory effect on nociception, and they were able to demonstrate that disinhibition of these neurons is central to the antinociceptive actions of opioids within the medulla.
Currently, they are interested in identifying neurotransmitters that activate these two cell classes differentially to promote or suppress pain. They are also interested in how this modulatory system is activated under physiological conditions, and are looking at the inputs from limbic forebrain structures such as the hypothalamus to the rostral ventral medulla in an attempt to investigate this issue.
Dr. Ingram's research is focused on understanding neuronal mechanisms of synaptic plasticity involved in pain and drug addiction circuits. One area of current research is focused on identifying intracellular signaling pathways involved in morphine tolerance and dependence using in vitro brain-slice recordings and in vivo behavioral assays. Our experiments focus on how mu opioid receptors (MOPrs) in the periaqueductal gray area (PAG) modulate neuronal excitability and synaptic transmission of PAG neurons. MOPrs are an integral part of the endogenous descending antinociceptive pathway that decreases pain impulses in the spinal cord. Repeated and continuous opioid administration induces neural changes in this system. We currently use whole-cell patch-clamp electrophysiological recordings, live-cell fluorescence imaging, immunohistochemical techniques, confocal microscopy, pharmacology and brain-slice and primary cultures of midbrain neurons for these studies.
Specific circuits within the CNS are dedicated to the maintenance of homeostasis and an optimal cellular environment through regulation of autonomic function. Disease states such as fever, obesity, diabetes, hypertension, autonomic hyperreflexia and cardiac arrhythmia are associated with altered regulation of the sympathetic outflow to cardiovascular and non-cardiovascular tissues.
Dr. Morrison's laboratory research uses electrophysiological and anatomical approaches to understand the functional organization, rhythmicities, developmental influences and pharmacology of the CNS circuits that regulate the sympathetic outflows controlling variables critical for homeostasis such as body temperature, energy expenditure, blood glucose, blood pressure, cardiac output and plasma catecholamines.