Transgenic Mice

As mentioned previously, the predominant form of LTP in the brain is dependent on the NMDA receptor. Functional NMDA receptors comprise more than one subunit and usually more than one type of subunit. For example, NMDAR1 subunits seem to be absolutely required for the survival of mice and are capable of assembling to form a working receptor. However, most receptors also contain NMDAR2 subunits, of which these are four different kinds (2A-2D). The NMDAR2 subunits do not form functional receptors on their own but modify the characteristics of NMDAR1 when they associate with it; each of the four subtypes combines with NMDAR1 to produce a receptor with slightly different characteristics. In the rat, NMDAR2A and NMDAR2B are strongly expressed in the hippocampus. The hippocampus has essentially no NMDAR2C (which is predominantly located in the cerebellum) or NMDAR2D (which is found in the thalamus and hypothalamus). Mice with targeted disruptions (knockouts) of NMDAR1 or NMDAR2B show no gross anatomical abnormalities in the brain but die after birth ofrespiratory failure and impairment of suckling response, respectively. Of the hippocampal NMDAR2s, electrophysiological studies suggest that NMDAR2B should be more effective than NMDAR2A in causing LTP. In a recent study, a transgenic mouse overexpressing the NMDAR2B was created and evaluated; the researchers called their transgenic "doogie" after a precocious fictional medical student Doogie Hauser. These mice show enhanced retention of spatial memory and of both context (hippocampal-dependent) and cued (hippo-campal-independent) fear conditioning, and they were dubbed "supermice" by the media. However, these mice show faster extinction (i.e., forgetting) of fear conditioning and enhanced novel-object exploratory responses, which are not traits likely to enhance survival in the wild. Between 20 days of age and adulthood, the amounts of NMDAR2A and NMDAR2B in the hippocampus decline slightly. A better name for this transgenic mouse might be Peter Pan since the decreased expression of the 2B subunit in adulthood is counteracted by overexpression, keeping the complement of 2B in a "child-like" state.

Breaking Bulimia

Breaking Bulimia

We have all been there: turning to the refrigerator if feeling lonely or bored or indulging in seconds or thirds if strained. But if you suffer from bulimia, the from time to time urge to overeat is more like an obsession.

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