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The orbitofrontal cortex (OBF) is known to play an important role in the central regulation of adaptive behavior. Previous studies provided evidence for feeding-associated neurons in the rodent and macaque OBF. To further elucidate functional attributes of these neurons, complex electrophysiological–neurochemical–behavioral studies were performed in rats and rhesus monkeys. Single unit activity was recorded in the rat and monkey OBF during microiontophoresis of glucose, various neurochemicals, as well as gustatory stimulations. To investigate feeding-related neuronal mechanisms at the cognitive level, recordings were also performed in the monkey OBF during a visual food discrimination task. OBF neurons displayed specific responsiveness to gustatory stimuli, as well as to microelectrophoretically applied chemicals. The majority of gustatory cells were shown to possess specific, feeding-related neurochemical attributes: microelectrophoretically administered glucose changed their firing rates. These chemosensory cells also displayed differential sensitivity to catecholamines and other neurochemicals. In the discrimination task, category-specific or task-specific neurons showed a broad variety of selectivity for food-related visual stimuli. Expectation- and reward-related activities were also recorded. Our results provide evidence that OBF neurons possess specific endogenous and exogenous chemosensitivity, and that they utilize differential neurotransmitter mechanisms in feeding-related cognitive functions. Thus, the complex network of these chemosensory neurons possesses broad ranging, multiple functional attributes in the homeostatic control.

The complex system of chemosensory neurons of the glucose-monitoring neural network (GMNN)–by integrating various feeding-associated exogenous sensory cues with endogenous humoral signals and with perceptual as well as motivational information–possesses multiple functional attributes in the homeostatic control. It is well known that pathophysiological processes (infections, tumors, injuries, etc.) alter defense and adaptive reactions of these control mechanisms. The so-called cytokines–and one of their major representatives the interleukin-1β (IL-1β) itself–are suggested to interact with the CNS and to play essential role in these above reactions. To elucidate the involvement of orbitofrontal cortical glucose-monitoring (GM) neurons in these functions, complex microelectrophysiological–neurochemical as well as behavioral–biochemical experiments were performed. The single neuron activity recording study demonstrated that high proportion of GM neurons in the rat orbitofrontal cortex (OBF) were shown to change their firing rate in response to the microelectrophoretically administered IL-1β. We also proved that IL-1β microinjection into the rat OBF resulted in the development of complex feeding and metabolic disturbances. Our findings, therefore, confirm that neocortically organized IL-1β-mediated adaptive reactions through orbitofrontal cortical constituents of the GMNN play important roles in the biologically adaptive central homeostatic control.