Houpt Lab

The lab has two major research foci: Conditioned Taste Aversion as a model for determining the molecular basis of learning, and the behavioral and neural effects of High Magnetic Fields, such as those used in MRI machines.

Here are the some of the experiments currently underway (as of February 2007):

Laser Capture Microscopy and AP-1 Family Expression

NMDA Receptors in Conditioned Flavor Taste Preference

D-Cycloserine Enhancement of Conditioned Taste Aversion

Time Course of Circling induced by High Magnetic Fields

Adaptation to the Effects of High Magnetic Fields

Laser Capture Microscopy and AP-1 Family Expression Bumsup Kwon, MS

A key problem in the study of learnin is that only a small number of neurons participate in the acquisition and consolidation of new memories. Many neurons rapidly produce c-Fos mRNA and protein after a stimulation such as a novel taste or injection of a toxin. We routinely use c-Fos to identify a sparse population of neurons within specific brain regions (amygdala, parabarachial nucleus, or nucleus of the solitary tract) that appear to particpate in CTA learning.   To find out what other genes are being expressed in the c-Fos positive cells, Bumsup is using an Arcturus laser capture microscope to collect individual cells out of the surrounding tissue.   Bumsup collects enough mRNA with only 100 cells to conduct about 10 RT-PCR reactions with diverse primers. His current focus is on the expression of other AP-1 family members (Fra2, c-Jun, etc.) that can dimerize with c-Fos to initiate target gene expression involved in memory consolidation.

NMDA Receptors in Conditioned Flavor Taste Preference (CFTP) Glen Golden

Learned flavor preferences are incredibly common, but understudied. Everyday examples include preferences for different foods, or learned preferences for innately unpalatable substances such as coffee or alcohol.   The neurobiological basis for CFTP learning is not well understood. Glen is using a simple protocol in which rats learn to prefer a particular flavor of Kool-Aid (e.g. cherry) that has been previously mixed with a highly palatable sugar (8% fructose), over a different Kool-Aid (e.g. grape) that is mixed with a less palatable sweetner (0.2% saccharin). When given a 2-bottle choice of cherry vs. grape Kool-Aid, both mixed with saccharin, the rats will choose to drink   the cherry previously paited with fructose. CFTP learning is very robust, and is apparently impervious to extinction (why bother to unlearn a preference for a good food?) Glen has found that CFTP learning requires NMDA receptor activation, because systemic injections of the antagonist MK-801 completely block CFTP learning. He is now trying to identify brain regions involved in CFTP using c-Fos and site-specific injections of NMDA agonists and antagonists.

D-Cycloserine Enhancement of Conditioned Taste Aversion Rachel Davenport, MS

NMDA receptors have been implicated in CTA before by others: injections of NMDA antagonists into the gustatory cortex or amygdala attenuate CTA, and within the gustatory cortex the NR2B subunit is phosphorylated in response to a novel taste. Activation of the NMDA receptor, however, requires both glutamate and the binding of a ligand to the glycine-binding site of the NR1 subunit. In the forebrain, the endogenous ligand is D-serine. D-serine is interesting because it is synthesized by glial cells, and its production may limit endogenous NMDA neurotransmission. We have found that exognenous administration of D-cycloserine enhances CTA learning. Rachel has further discovered that D-cycloserine does not enhance long-delay CTA learning. Currently, Rachel is using chiral HPLC to determine the time course of D-serine synthesis in the gustatory cortex and amygdala.  

Time Course of Circling induced by High Magnetic Fields Chuck Houpt.  

After exposure to static magnetic fields of 4T or above, rodents walk in circles (they circle more as the magnetic field strength increases, and as the duration of exposure increases.)   In order to determine the duration of locomotor circling and any lingering after-effects of exposure on locomotion, we are quantifying the swimming patterns of mice at various time points after 14T exposure. Mice are exposed for 30 min to 14T, and then placed in a heated 2-m diameter swimming pool for 2-min. Because mice try to make a straight bee-line for the side of the swimming pool, this is a pretty sensitive measure of vestibular disturbance: magnet-exposed mice start swimming in wide circles, alternating with tight circles. By asking mice to swim 1 min, 5-min, 10 min, 20 min after exposure, we hope to observe the decay of the magnet-induced vestibular disturbance. Chuck is writing the software to track the mice within QuickTime movies of the swimming sessions, and thus analyze the angular speed of the mice.

Adaptation to the Effects of High Magnetic Fields

After exposure to magnetic fields, rodents walk in circles and can acquire a CTA. In our earlier studies, we consistently noticed that rats and mice circle most after their first exposure, and less on the second and third exposures to the magnetic field.   There are two possibilites as to why the magnetic field has less effect after repeated exposures: either the rats are habituating to the effect of the magnetic field (as commonly happens with vestibular stimulation), or repeated exposure can cause damage to the vestibular system resulting in a diminished response.   We are testing these hypothesis by determining the parameters of exposure that cause desensitization, e.g. exposing rats multiple times on a single day, or exposing the rats multiple times across weeks or months. We're evaluating the response of the rats by obsesrving locomotor circling, CTA expression, and soon by testing vestibular function when walking a tightrope or while swimming.