Nk1 receptors within emotional and autonomic centers of the brain migrate in response to both emotional and physiological stress, Cornell neuroscience professor Andree Lessard said this past Wednesday at the Dartmouth-Hitchcock Medical Center physiology seminar.
The Tachykinin or Nk family of receptors can be found distributed throughout both the central nervous system (CNS) and the peripheral nervous system (PNS). There are three primary receptor-subgroups with this family: Nk1, Nk2, and Nk3. Unlike the other two receptors, the Nk1 subgroup exists in significant number throughout both the PNS and the CNS. Lessard’s research focuses on two key regions within the CNS: the basolateral amygdala and the nucleus tractus solitarius (NTS).
The basolateral amygdala, found in the brain’s limbic system, provides the initial integration of emotionally stressful stimuli. Lessard examined the effects of emotional stress on the localization of Nk1 receptors within neurons of this region, before and after the stress exposure. To induce emotional stress within the rats, the experiment utilized an “acoustic startle,” exposing the animals to extremely loud bursts of quick noise.
Immuno-gold electron microscopy showed a significant shift in the Nk1 receptor density away from the plasma membrane of the neurons and into cytosolic compartments. These results indicate Nk1 receptor internalization following intense emotional stress, Lessard said.
Lessard found similar results when rats were exposed to physiological stress. She exposed the experimental group to hypoxic (10% oxygen) conditions to activate the chemosensory pathway. Many afferent neurons from this pathway innervate key regions of the nucleus tractus solitarius (NTS) when exposed to physiologically stressful conditions.
The results were more nuanced. After 10 days, rats exposed to intermittent chronic hypoxia demonstrated a significant decrease in cytosolic Nk1 receptors, though many of the plasma membrane receptors remained intact. However, 35 days post-treatment, Nk1 receptor density in both the plasma membrane and cytosolic compartments decreased dramatically.
Critically, this change in Nk1 receptor density after hypoxia was exclusive to small distal dendrites of the axon: the areas most likely to be innervated by afferent chemo-sensitive neurons. However, there was no change in receptor density in the medium dendrites which serve as a bridge between the distal dendrites and the soma. This may be indicative not of Nk1 trafficking, but rather a down-regulation of Nk1 receptor function. The effect also seems isolated to the NTS since the adjacent trigeminal nucleus did not see a similar decrease in Nk1 density.
Further studies are needed to delineate the exact relationship between Nk1 receptors and the stress response, Lessard said.