Neural network interactions and ingestive behavior control during anorexia

Abstract

Many models have been proposed over the years to explain how motivated feeding behavior is controlled. One of the most compelling is based on the original concepts of Eliot Stellar whereby sets of interosensory and exterosensory inputs converge on a hypothalamic control network that can either stimulate or inhibit feeding. These inputs arise from information originating in the blood, the viscera, and the telencephalon. In this manner the relative strengths of the hypothalamic stimulatory and inhibitory networks at a particular time dictates how an animal feeds. Anorexia occurs when the balance within the networks consistently favors the restraint of feeding. This article discusses experimental evidence supporting a model whereby the increases in plasma osmolality that result from drinking hypertonic saline activate pathways projecting to neurons in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA). These neurons constitute the hypothalamic controller for ingestive behavior, and receive a set of afferent inputs from regions of the brain that process sensory information that is critical for different aspects of feeding. Important sets of inputs arise in the arcuate nucleus, the hindbrain, and in the telencephalon. Anorexia is generated in dehydrated animals by way of osmosensitive projections to the behavior control neurons in the PVH and LHA, rather than by actions on their afferent inputs.

Figure 1

Parts of the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) are critical nodes in the a hypothalamic controller for ingestive behavior [Swanson, 2000]. In this model, feeding, together with its coordinated autonomic motor events, is controlled by their extensive projections to the telencephalon and hindbrain.

Figure 2

The hypothalamic ingestive behavior controllers in the paraventricular nucleus of the hypothalamus (PVH) and lateral hypothalamic area (LHA) illustrated in Figure 1 receive a variety of inputs from regions that can influence feeding behavior. Three examples are illustrated here. Group A inputs from the arcuate nucleus (ARH) contain neuropeptide Y (NPY), agouti-related peptide (AgRP) and _-MSH. In turn, ARH neurons are regulated by humerosensory information in the form of leptin and insulin. Group B inputs originate in the hindbrain and convey a range of viscerosensory information from the gastrointestinal tract, liver, hepatic portal vein, etc. Nor-epinephrine (NE), epinephrine (E), and NPY are important constituents of these projections. Group C inputs constitute a complex set of projections from the telencephalon that convey cognitive influences on feeding behavior. Swanson [10] has proposed that these projections take the form of a triple descending pathway from the cortex (glutamate), striatum (GABA), and pallidum (GABA).

Figure 3

Intravenous injections of 2-deoxy-D-glucose (2DG) in euhydrated control rats leads to increased feeding (A), hyperglycemia (B), and elevated plasma corticosterone concentrations (C). In animals dehydrated by drinking 2.5% hypertonic saline for 5 days only the feeding response to 2DG is suppressed. In these same animals, the hyperglycemic and plasma corticosterone responses remain intact (Data adapted from [30])

Figure 4

The difference between the 4 hour feeding response of individual animals injected with 1μg of neuropeptide Y in the lateral hypothalamic area in the euhydrated state and then injected again later in the dehydrated state (after drinking 2.5% hypertonic saline). The data show that the suppression of NPY-induced feeding is inversely correlated to the intensity of the anorexia that develops as a consequence of dehydration (Data adapted from [32]).

Figure 5

The 30 minute feeding response to 50ng of muscimol injected bilaterally into the shell of the nucleus accumbens of dehydrated by drinking 2.5% hypertonic saline is inversely correlated to the intensity of the resulting anorexia (Data adapted from [36]).

Figure 6

A) Ingestive behavior control is thought to be controlled by a brain-wide network that converges onto a motor control network, which is organized at three levels [adapted from 10,11,12,18]: A hypothalamic behavior controller that contains drive circuits that can either stimulate, or inhibit behaviors; action selection networks that integrate the outputs of the hypothalamic controller with those of other systems; and executive pre-motor and motor neuron networks. The generation of motivated behavioral actions by motor control networks can be initiated by a variety of inputs. The three examples are shown in Figure 2 are reproduced here. They are: A, inputs from the arcuate nucleus (ARH) that are regulated by humerosensory information;. B, inputs originating in the hindbrain that convey a range of viscerosensory information; and C, inputs from the telencephalon that convey cognitive influences on feeding behavior. B) Evidence discussed in this article suggests that the increased osmolality that results from dehydration acts at the level of the hypothalamic behavior controller to suppress the actions of the inputs A) – C), which in turn generates anorexia.