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Hypothalamus

Divisions and Definitions || Important Nuclei || How It's All Hooked Up
What Does It All Mean? || Overview || References and Resources || Comment

Divisions and Definitions

The hypothalamus is a small structure sandwiched between the pituitary below and the thalamus above (hence the term "hypo"-thalamus). It has visceral, autonomic, endocrine, and emotional functions.

The hypothalamus is classically divided into three regions: anterior, tuberal, and posterior. These divisions are split into a medial and lateral half by the columns of a structure known as the fornix.

There are nuclei (ie: a collection of neurons) within each division that perform specific functions. Depending on what anatomy book you read, the list of nuclei can be long and extensive, and frankly, it is worthless to try and memorize all of them. That being said, some of the nuclei are well understood and perform vital functions. We will limit our discussion to these nuclei and their connections.

The "Important" Nuclei

The nuclei of the antero-medial hypothalamus include the medial preoptic nucleus, supraoptic nucleus, paraventricular nucleus, anterior nucleus, and suprachiasmatic nucleus.

The medial preoptic nucleus secretes hormones responsible for sexual development (ie: gonadotropins like leutinizing hormone (LH) and follicle stimulating hormone(FSH)). The supraoptic and paraventricular nuclei secrete antidiuretic hormone (ADH) and oxytocin; the paraventricular nucleus also secretes "releasing" hormones like corticotropin releasing hormone (CRH) that influence the anterior pituitary gland. The anterior nucleus is important in temperature regulation (specifically, helping the body cool down). The suprachiasmatic nucleus plays an important role in circadian rhythms and regulating the sleep-wake cycle.

The tubero-medial hypothalamus contains the dorsomedial nucleus, ventromedial nucleus, and arcuate nucleus. The most well understood of these nuclei is the arcuate nucleus. It releases dopamine, as well as most of the releasing hormones (ie: CRH, TRH, GHRH, etc.) that influence the anterior pituitary gland. The dorsomedial and ventromedial nuclei are important in signaling satiety.

The postero-medial hypothalamus contains the mammillary bodies and the posterior nucleus. The mammillary bodies are important in linking the hippocampus to the hypothalamus and thalamus. This is described in more detail on our section regarding the limbic system. The posterior nucleus also helps control body temperature (specifically, helping the body warm up).

The lateral nuclear group of all three divisions (anterior, tuberal, and posterior) are important in signaling hunger. They also perform other functions, but the localization of these functions is not well understood.

How It's All Hooked Up

The hypothalamus communicates with many areas of the brain. These connections can be described as either afferent (ie: coming into the hypothalamus) or efferent (ie: leaving the hypothalamus). As you read the following, it is important to note that these connections are far more complex than described...

The Inputs (Afferents)

A structure known as the amygdala forms many connections with the hypothalamus. Two important fiber pathways known as the stria terminalis and the ventral amygdalofugal tract send information to the hypothalamus. The stria terminalis connects the amygdala to the anteromedial nuclei. The ventral amygdalofugal tract connects the amygdala to the lateral hypothalamus. There are also additional "direct" connections between the amygdala and the hypothalamus.

The amygdala acts as a relay station that takes information from numerous areas (ie: prefrontal cortex, olfactory cortex, brainstem structures) and passes it along to other brain structures like the hypothalamus. The best description of the amygdala that I have come across is the following: the amygdala links subjective "feelings" to the drive related behavior patterns controlled by the hypothalamus, which occurs in the setting of learned facts stored in the hippocampus.

The medial forebrain bundle (MFB) is a fiber tract that courses through the hypothalamus forming many afferent and efferent connections along its path. It primarily connects the septal nuclei (which receive input from the amygdala) and olfactory regions of the brain to the hypothalamus.

The hippocampus sends many fibers to the hypothalamus via a large white matter tract known as the fornix. The fornix splits into pre-commissural and post-commissural fibers. The pre-commissural fibers connect to the septal nuclei (and then to the hypothalamus via the medial forebrain bundle) and the preoptic nuclei. The post-commissural fibers connect to the mammillary bodies.

Brainstem structures also connect to the hypothalamus. A midbrain structure known as the periaqueductal gray sends information via a fiber tract known as the dorsal longitudinal fasciculus (DLF). Another brainstem structure, the solitary nucleus, which receives taste and visceral information from the tongue and body sends info via the DLF and MFB to the hypothalamus. More specifically, the rostral solitary nucleus (aka: medial parabrachial nucleus) sends taste information and the caudal solitary nucleus (aka: lateral parabrachial nucleus) sends information about visceral sensations (ie: "my gut is hurting").

And last, but not least, the retina sends information to the suprachiasmatic nucleus to help regulate sleep cycles. Confused yet??? Hopefully the image below will help clarify a little...

Hypothalamus Connections

The Outputs (Efferents)

It's your lucky day! The efferent pathways, for the most part, are exactly the same as the afferent pathways. Most of the above structures have reciprocal connections with the hypothalamus. They send info to the hypothalamus, the hypothalamus processes it, and sends information back.

Hold your horses though! There are a couple of important efferent connections that we haven't mentioned yet...

The first is the tuberohypophyseal tract. This tract is composed of axons from the paraventricular and arcuate nuclei. These axons end in a region known as the median eminence, which is near the pituitary gland. Hormones (specifically, pituitary releasing hormones like CRH, TRH, GHRH, dopamine, etc.) synthesized in the paraventricular and arcuate nuclei are shipped down the tuberhypophyseal tract and are released into the hypophyseal venous portal system. The hormones travel towards the anterior pituitary gland and influence the release of many other hormones that control bodily functions (think thyroid gland, adrenal gland, testicles, and ovaries).

The second important efferent pathway is the supraopticohypophyseal tract. This tract is composed of axons from the paraventricular and supraoptic nuclei. If you remember from our discussion above, these nuclei synthesize, and secrete, antidiuretic hormone (ADH) and oxytocin. However, rather than stopping in the median eminence, these axons travel down the pituitary stalk and terminate in the posterior pituitary gland. The hormones are then released into the blood stream to perform their specific functions.

What Does It All Mean?

Damage from brain tumors, inflammation, or strokes can cause different clinical problems depending on the area of the hypothalamus involved. Let's discuss some of these functional regions in more detail...

The antero-medial region of the hypothalamus can be thought of as the parasympathetic control system of the brain. It's main function is to help dissipate heat via sweating and blood vessel dilation. Injury to this region can cause hyperthermia (ie: inability to dissipate heat).

Along the same lines, the postero-lateral hypothalamus is the sympathetic control center. Its main job is to help conserve heat via shivering and cutaneous blood vessel constriction. Therefore, injury to this region can cause hypothermia.

Interestingly, lesions in the posterior hypothalamus typically injure both the parasympathetic and sympathetic efferent fibers destined for the brain stem and spinal cord. As a result, a condition known as poikilothermia occurs, in which body temperature is entirely dependent on the environmental temperature.

The ventro-medial portion of the hypothalamus signals satiety. If this aspect of the hypothalamus is injured you never feel full. This can cause profound obesity. Along similar lines, the tubero-lateral region of the hypothalamus is concerned with signaling hunger. Therefore, lesions in this region result in starvation.

Injury to the supraoptic or paraventricular nuclei can affect the function of the posterior pituitary leading to a condition known as diabetes insipidus.

In actuality, injury to specific sub-sections of the hypothalamus are rare. Usually, multiple areas of the hypothalamus are involved. Global hypothalamic injury is typically fatal.

It is important to note that injury to only one of these areas is exceedingly rare in clinical practice. In fact, most of these are based on specific lesions performed in laboratory mice and rats. Therefore, the clinical presentation in patients with hypothalamic dysfunction is more variable.

Overview

The hypothalamus is one complicated brain structure! It integrates and coordinates signals from the body and other parts of the brain to drive behavior and coordinate autonomic and endocrine functions. The hypothalamus can be anatomically and functionally sub-divided.

References and Resources

(1) Baehr M, Frotscher M. Duus' Topical Diagnosis in Neurology: Anatomy, Physiology, Signs, Symptoms. Fourth Edition. Stuttgart: Thieme, 2005.

(2) Purves D, Augustine GJ, Fitzpatrick D, et al. Fourth Edition. Sinauer Associates, Inc., 2007.

(3) Hagiwara D, Arima H, Morishita Y, et al. Arginine vasopressin neuronal loss results from autophagy-associated cell death in a mouse model for familial neurohypophysial diabetes insipidus. Cell Death Dis. 2014 Mar 27;5:e1148.

(4) Peppa M1, Papaxoinis G, Xiros N, et al. Panhypopituitarism due to metastases to the hypothalamus and the pituitary resulting from primary breast cancer: a case report and review of the literature. Clin Breast Cancer. 2009 Nov;9(4):E4-7.

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