Circuitry Of The Hypothalamus.docx

Circuitry of the Hypothalamus The hypothalamus has the most complex circuitry of any brain region. Like other brain areas there are neural interconnections. But unlike other brain areas, there are also extensive non-neural communication pathways between the hypothalamus and other brain regions and the periphery. Neural Connections. The most noteworthy (and complex) feature of the neural connections of the hypothalamus is that except for a few exceptions, they are extensively bi-directional. Limbic Circuits. These pathways are essential for the normal expression and control of emotions, learning and reproductive behavior. The bi-directional (afferent and efferent) pathways include the medial forebrain bundle, the fornix, the stria terminalis and the ventral amygdalofugal pathway. The medial forebrain bundle interconnects basal forebrain structures including the septal nuclei and ventral striatum with hypothalamus and structures in the brainstem tegmentum including the locus ceruleus, the parabrachial nucleus, dorsal motor nucleus of the vagus. The fornix interconnects the hippocampal formation to the septal, preoptic and medial mammillary nuclei. The stria terminalis interconnects the amygdala to the septal region and the hypothalamus especially, the preoptic and ventromedial regions. Finally, the ventral amygdalofugal pathway interconnects the amygdala, especially the central amygdaloid nucleus with the septal region and the preoptic areas of the hypothalamus. In addition to these bidirectional pathways, there are also two unidirectional efferent limbic pathways from the hypothalamus. The mammillo-thalamic tract projects from the mammillary nuclei to the anterior nucleus of the thalamus. The anterior nucleus of the thalamus in turn projects to the cingulate cortex, which completes the circuit of Papez by projecting back onto the subiculum of the hippocampus. The circuit of Papez was the first circuit proposed to mediate emotions and still is considered one of the chief circuits of the limbic system. The mammillo-tegmental tract projects from the mammillary nuclei to the brainstem tegmentum and as far caudal as the lateral gray of the spinal cord. Sensory and Autonomic Circuits. These pathways provide visceral and somatosensory input to the hypothalamus and output of the hypothalamus to control the autonomic nervous system. These pathways are especially important for the control of feeding, insulin release and reproduction. The bi-directional pathways in this circuitry include the medial forebrain bundle noted as part of limbic circuitry above, as well as the dorsal longitudinal fasciculus. Whereas the medial forebrain bundle runs laterally through the brainstem and hypothalamus, the dorsal longitudinal fasciculus runs medially through the periventricular and periaqueductal gray matter. Both pathways bring visceral and somatic input to the hypothalamus from the nucleus of the solitary tract, the parabrachial nuclei, the reticular formation and the periaqueductal gray. The medial forebrain bundle also brings monoaminergic fibers containing noradrenaline and serotonin into the hypothalamus from various brainstem nuclei including the raphe nuclei that have key roles in modulating neuroendocrine functions. More rostral projections of these monoaminergic fibers as well as peptidecontaining efferent fibers that originate in the hypothalamus and join the medial forebrain bundle as it ascends into the orbital cortex, insula and frontal cortex are involved in the control of motivation. Descending efferent projections of the

hypothalamus through these pathways terminate on parasympathetic nuclei of the brainstem such as the dorsal motor nucleus of the vagus. Unidirectional afferent input to the hypothalamus is derived from the spinohypothalamic tract and the retino-hypothalamic tract. The spinohypothalamic tract is a component of the anterolateral system of somatosensory fibers that also includes the spinothalamic tract and provides input concerning pain as well as input necessary for orgasm. The retino-hypothalamic tract provides input to the suprachiasmatic nucleus that is used to entrain circadian rhythms to the light-dark cycle. Finally, unidirectional efferent pathways from the hypothalamus include the hypothalamo-spinal tract, which projects onto brainstem and finally spinal preganglionic sympathetic and parasympathetic neurons in the spinal intermediolateral cell column, and a histamine projection to thalamus and cortex from the inferior lateral tuberal region that regulates the sleep-wake cycle. Neuro-Humoral Connections. Unlike any other brain structure the hypothalamus both sends and receives information by way of the blood stream. There are two pathways that comprise the neuro-humoral connections of the hypothalamus. The Pituitary. These pathways include the hypophyseal-portal system of blood vessels that surround the median eminence, the infundibulum and pituitary gland. The details of this system in neuroendocrine function will comprise the third chapter of this section.

Figure 1.7

Circumventricular Organs. There are several sites at which the blood brain barrier is highly permeable and at which specific transporters are present that allow passage of chemosensory stimuli from the blood into the brain. For example, the organum vasculosum of the lamina terminalis is the site at which pyrogens such as interleukin-1 and tumor necrosis factor bind to receptors that transport these molecules into the CNS and initiate the central synthesis of prostaglandins. These in turn act on the anterior nucleus to initiate a change in body temperature set-point resulting in fever. Passage of hormones through both the organum vasculosum and the median eminence is essential for normal feedback on the hypothalamus for neuroendocrine control. The area postrema is the location of the chemotoxic trigger zone at which emesis is induced by various toxins in the blood stream and that affect the hypothalamus to induce taste aversion. Passage of peptides through the subfornical organ are thought to participate in mechanisms of learning, while passage of signals through the pineal body affects circadian and circannual timing patterns.

Homeostasis is the process by which a steady state of equilibrium, or constancy, in the body with respect to physiological functions and chemical compositions of fluids and tissues is maintained. Physiological set points refer to the baseline level at which functions such as heart rate, and at which chemical compositions such as plasma sodium concentration are normally maintained. These set points are represented in the brain by specific discharge rates in neurons dedicated to the monitoring and control of

specific physiological processes. Thus, separate groups of neurons are dedicated to the control of heart rate, temperature, etc., by their set point discharge rate. The hypothalamus has the greatest concentration of nuclei at which set points are encoded, monitored and controlled, and so can be considered as the key brain region for the control of homeostasis. Specific receptors and sensors throughout the body detect disruptions in the normal balance of body functions and chemistry that are produced by stress stimuli that can range from injury or infection to pain and emotional distress. These data are transmitted to the central nervous system and affect the discharge rate of set point neurons in hypothalamic nuclei (Figure 1.1). These changes in discharge rate result in altered hypothalamic efferent outflow and hence change in the functions of regulatory systems that counteract the stress stimulus and restore homeostasis. These effects include alterations in the functions of the autonomic nervous system, endocrine and immune systems, as well as alterations in behavior by hypothalamic influences on limbic brain circuitry. Each of the target systems influenced by the hypothalamus return feedback controls onto the hypothalamus completing a circuit and so establishing a homeostasis system.