br Additional implications cell ensembles

Additional implications- cell ensembles While there are three electrophysiological types of PPN Asiatic acid in vitro, each of these is represented in the N-only, P/Q-only and N+P/Q cell groups, suggesting that all of the electrophysiological cell types are found in each cell ensemble. Anatomically, neurons in the PPN are scattered such that in the pars compacta there are glutamatergic (GLU), cholinergic (ACh), and GABAergic neurons in the ratio of 5:3:2, respectively [13]. Since all three electrophysiological types are included in the calcium channel segregation, it also means that all of the transmitter types are represented in the calcium channel segregation. This suggests that there are ensembles of N-only cells with glutamatergic, cholinergic, and GABAergic cells, and similarly for P/Q-only and N+P/Q cells. Studies using calcium imaging in the PPN pars compacta reveal an interesting anatomical organization within the nucleus. Pairs of PPN cells are labeled throughout the nucleus even in the control, unstimulated condition [48]. The spatial separation between couplets suggests that there are clusters of cells throughout the nucleus. Since electrically coupled neurons generally represent GABAergic neurons, we speculate that there are 5 GLU and 3 ACh neurons closely associated with each GABAergic pair. That is, there may be clusters of approximately 10 neurons scattered within the pars compacta that may create a functional subgroup. These functional subgroups may each bear a different combination of calcium channels. Much additional evidence is required to support this hypothesis, but it may be possible to dissect such an organization to determine how the nucleus as a whole generates coherent activity at specific frequencies. It is also important to determine how PPN neurons respond to sensory input and how that input generates coherent activity. Fig. 4 provides a proposed organization for these groups, each of which would includes each transmitter type, but all of the cells within the group would express one or both of the channels. Similar functional clustering has been proposed for the hippocampus, especially in relation to epileptic networks [50]. In a study of cell assemblies in the hippocampus, Buzsaki described subsets of about 10 neurons that showed repeated synchronous firing during open field exploration [51]. Interestingly, the timescale of activity between these neurons had a median of 23ms, and the peak optimal timescale was ~16ms, that is, most activity occurred in the 40–60Hz range. We hypothesize that a similar temporal relationship will be evident among cell clusters in the PPN. Moreover, we postulate that there are cell ensembles of 5 GLU, 3 ACh, and 2 GABA cells all of which have N-only calcium channels, representing a cluster firing during REM sleep only (REM-on cluster), and similar ensembles which have only P/Q-type channels that fire only during waking (Wake-on cluster), and ensembles which have both N- and P/Q-type calcium channels that fire during waking and REM sleep (Wake/REM-on clusters). We proposed that each ensemble manifests N-only, P/Q-only, or both N+P/Q calcium channels [2].
Conclusion The implications of the discovery of gamma band activity as a ubiquitous mechanism in RAS nuclei that modulate waking and REM sleep, and activate the cortex as well as postural and locomotor systems, are of critical importance. The fact that these centers can generate gamma band oscillations, however, should not be surprising given the descriptions of gamma activity in other subcortical structures such as the cerebellum, hippocampus, and the basal ganglia. Moreover, gamma band activity between these regions is coherent, so that RAS gamma band activity is probably highly coordinated with cortical and other subcortical gamma band generators, depending on the task. This also should not be surprising, given the need for reverberating circuits and cell assemblies essential for the persistence or maintenance of processes that mediate perception, movement, learning, and memory. These issues are discussed at length in a recent book [2]. The process of maintaining gamma band activity is metabolically demanding. PPN neurons must remain highly active during the waking state. Waking is hard work. When these neurons are over active, the consequences are wide-ranging and exhausting, in keeping with the consequences of increased waking drive in insomnia and sleep-deprivation symptoms. This review strengthens the need to revisit the physiological mechanisms governing the wake/sleep cycle because of the impact it could have on a number of psychiatric and neurological disorders.