Mutual inhibitory model

Figure 2.4 Flip-flop switch model of wake and slow wave sleep active systems. Mutually inhibitory connections exist between GABAergic/Galaninergic slow wave sleep active neurons in the ventrolateral preoptic area (VLPO) of the anterior hypothalamus and aminergic neurons in the hypothalamus (histamine (HA) neurons in the tuberomammillary nucleus (TMN)) and brainstem (serotonin (5-HT) neurons in the dorsal raphe (DR) and noradrenaline (NA) neurons in the locus coeruleus (LC)). Orexinergic neurons in the perifornical hypothalamus (PFH) stabilize the waking state via excitation of the waking side of the flip-flop switch (aminergic neurons).

The nonobese diabetic mouse (NOD), as well as the biobreeding (BB) rats are the two rodent models whose diabetes-related immunopathology is considered to be quite similar to that in humans. Studies in these animal models have revealed that autoreactive T cells that mediate islet 8 cell destruction belong to the Thl subset of T cells (produce IL-2 and IFN-7), whereas regulatory T cells are of the Th2 type (produce IL-4 and IL-10). Because Thl and Th2 cells are mutually inhibitory, there have been many trials using IL-4 and/or IL-10 for the prevention of autoimmune disease, like autoimmune diabetes, rheumatoid arthritis (Evans et al., 1996 Boyle et al., 1999), and inflammatory bowel disease (Rogy et al., 2000). 

In Section II, we demonstrate this approach with an equation that incorporates a nonlinear Hill function to model genetic control representing a mutually inhibitory network of two elements [26], and an inhibitory loop of three elements [27]. Although theoretical models of these types of networks have been known for at least 30 years [20, 32, 33], they took on new life in 2000 with the construction of genetic regulatory circuits in bacteria that were well described by the equations. 

Reilly (37) pointed out another set of complications that often affect commensal systems this was suggested by some experiments performed by Chao and Reilly (38). The complications that Reilly mentioned arise from the production of metabolic by-products by the commensal population that have effects, either stimulatory or inhibitory, on the host population. The production of such substances changes the interaction of pure commensalism into an Interaction of pure mutualism or protocooperation, or into a combination of commensalism and amensallsm. Reilly presented computer solutions of the differential equations for various model systems of this type, and more recently Sheintuch (39) made a detailed analysis of commensal systems complicated by the production of substances having inhibitory effects. 

Respiratory rhythmicity is an emergent property of the RCPG resulting from mutual inhibition of inspiratory and expiratory related neurons. A minimal model due to Duffin [1991] postulated the early-burst inspiratory (I) neurons and Botzinger complex expiratory (E) neurons to be the mutually inhibiting pair. Adaptation of the I neurons (e.g., by calcium-activated potassium conductance) results in sustained relaxation oscillation in the network under constant chemical excitation. Both neuron groups are assumed to have monosynaptic inhibitory projections to bulbospinal inspiratory (Ir) output neurons (Figure 11.3). The model equations are ... 

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