1. Focal Gene Deletion In The Brain (Knockout Of The Adenosine Al Receptor And N-Methyl-D-Aspartate Receptor (NMDAR) In Adult Mice Using Adeno-associated Viral Vector) To Study The Role Of Adenosine In Wake/sleep Transition 2. The Corelation Between Serot

Focal gene deletion in the brain (knockout of the adenosine A1 receptor and N-Methyl-D-Aspartate receptor in adult mice using adeno-associated viral vector) to study the role of adenosine in wake/sleep transitionIn humans, insomnia is endemic to modern society and can severely impair cognitive performance and the ability to accomplish daily tasks. Further, the ensuing problem of chronic sleep deprivation-induced stress is now only beginning to be appreciated as a major medical problem. Thus, it is important to understand physiological behavioral state transition from waking to sleep as a foundation for examination of the dysfunctional transition of insomnia.Adenosine (AD) appears to subserve a number of diverse roles in normal physiology, which include promoting and/or maintaining sleep. An increase in extracellualr AD in cholinergic arousal centers can facilitate a transition from waking to sleep. The adenosine exerts its inhibitory effect through activation of both pre-synaptic and post-synaptic adenosine A1 receptors (A1R's). Thus, A1 receptors play an important role in promoting sleep. The laterodorsal tegmentum (LDT) neurons supply most of the cholinergic tone to the brainstem and diencephalon necessary for physiological arousal. It is known that application of adenosine in the LDT nucleus increases sleep in vivo and directly inhibits LDT neurons in vitro by activating postsynaptic adenosine A₁ receptors.Furthermore, it has been shown that activation of ionotrophic glutamate receptors causes release of AD from cortical neurons. Low-level activation of the N-Methyl-D-Aspartate receptor (NMDAR) by glutamate or NMDA can cause the release of sufficient AD to exert a transient A1R-dependent inhibition of synaptic activity in the hippocampus. It has been observed NMDAR-dependent responses in the LDT and pharmacologically identified glutamate synaptic activity that may be inhibited, pre-synaptically by AD. It remains to be examined whether NMDAR activation is sufficient to exert a similar AD-mediated inhibition in the LDT, which affect sleep/wake states in a manner that is closely related to glutamate-mediated afferent input.So, in order to study the insomnia, it is necessary to study the relationship between genes of adenosine A1 receptor and NMDAR receptor in hippocampus and LDT and wake/sleep transition.Targeted gene disruption techniques are powerful tools to discover the functional roles of genes. Traditional knockout techniques produce animals lacking a gene in all cell types, hampering the identification of the gene's role in specific cells. In addition, lack of a gene early in development can produce severe behavioral abnormalities or result in the activation of compensatory mechanisms that obscure the normal functions of that gene. To overcome these obstacles, several researchers have created techniques to produce conditional gene deletions that occur in particular cell types at specific times. This...