L75. Neuroscience - Hypothalamus

• The hypothalamus integrates viscerosensory information to ensure homeostasis.
• The hypothalamus exerts control over endocrine and autonomic systems, influencing every organ in the body.
• The hypothalamus regulates fluid and electrolyte balance, food ingestion, energy metabolism, body temperature, hormonal balance, and reproduction.
• The hypothalamus influences motivated behaviors associated with feeding, drinking, temperature regulation, and reproduction.
• The hypothalamus weighs 4g (<0.3% of the entire brain) and is critical to life.

Anatomy

• Anterior: optic chiasm
• Middle: infundibulum
• Posterior: mammillary bodies
• The fornix courses through the hypothalamus to the mammillary bodies.
• The fornix divides each hypothalamic division into medial and lateral areas.
• Each medial and lateral area contains functionally distinct cell groups or nuclei.
• Connections between nuclei allow functional integration to feed coupled with autonomic functions.

Hypothalamic Nuclei

• Anterior Division (level of the Optic Chiasm):
  • Preoptic Area (POA)
  • Suprachiasmatic Nuclei (SCN)
  • Supraoptic Nuclei (SON)
  • Paraventricular Nuclei (PVN)
• Middle Division (level of the Infundibulum):
  • Arcuate Nucleus (ARC)
  • Ventromedial Nucleus (VM)
  • Dorsomedial Nucleus (DM)
  • Lateral Hypothalamic Area (L)
• Posterior Division (level of the mammillary bodies):
  • Mammillary Bodies (MB)
  • Posterior Nucleus (P)
    • Tuberomammillary Nucleus (TM)

Hypothalamic Control of the Autonomic Nervous System

• Hypothalamic stimulation evokes autonomic responses like heart rate and blood pressure changes, bladder contraction, intestinal motility, and piloerection.
• Afferent information about organ function arrives to the hypothalamus from multiple sources, including circumventricular organs and the reticular formation.
• The solitary nucleus in the medulla is a main source of visceral afferent information.
• The caudal part of the solitary nucleus collects afferent information from the cardiopulmonary system and abdominal viscera.
• The hypothalamus regulates sympathetic (SANS) & parasympathetic (PANS) autonomic nervous systems by projecting directly to preganglionic autonomic nuclei in the brainstem and spinal cord.
  • Dorsal Motor Nucleus of X of the Medulla (PANS)
  • Intermediolateral Cell Column of the Spinal Cord (SANS)
• Descending hypothalamic axons travel in the dorsolateral tegmentum of the midbrain, pons, and medulla.
• The Wallenberg lesion disrupts descending hypothalamic axons, causing Horner's Syndrome.
• The anterior hypothalamus exerts greater control over the PANS, while the posterior hypothalamus controls the SANS.

Hypothalamic Control of Body Temperature

• Temperature regulating cells are in both anterior & posterior hypothalamus.
• Stimulation of the anterior hypothalamus lowers body temperature via surface vasodilation (and panting in lower animals).
• Stimulation of the posterior hypothalamus elicits vasoconstriction, shivering, and piloerection, which raise body temperature.

Hypothalamic Control of Thirst

• Thirst is regulated by vascular volume and tissue osmolarity.
• Volume receptors are located in the heart and great vessels.
• Volume receptors sends information to the anterior hypothalamus via the solitary nucleus.
• Hypothalamic SON/PVN are efferent regulators of thirst.
• SON/PVN vasopressin neurons contain osmoreceptors that detect sodium levels and respond directly to changes in tissue osmolality.
• These neurons are tonically active and maintain a spontaneous firing pattern responsible for basal levels of circulating vasopressin.
• During dehydration, these neurons fire more rapidly and release ADH (vasopressin).

Hypothalamic Control of Feeding Behavior

• Feeding is controlled at mid-hypothalamic levels by ARC, VM, and LAT nuclei.
• Destruction of ventromedial hypothalamic region causes hyperphagia.
  • This are is called the satiety center.
• Destruction of the lateral hypothalamic area called causes aphagia.
  • This are is called the feeding center.
• Cells of the arcuate nucleus possess leptin receptors.
  • Arcuate nucleus uses neuropeptides to stimulate the lateral hypothalamus, which increases the circuit to increases feeding desire.
  • The ventromedial hypothalamic nucleus also participates.
• Gastrointestinal signals for gut distension and digestion of certain foods are transmitted by the vagus nerve to the solitary nucleus and then relayed to mid-hypothalamic levels.
• The arcuate nucleus senses a rise in blood leptin levels.
• The arcuate nucleus then releases specific neuropeptides to inhibit the lateral hypothalamus to stop feeding.
• Cell groups of the hypothalamus regulate intake of certain types of foods (fat, carbs, proteins).
• Certain neuropeptide transmitters in the hypothalamus are linked to cravings.

Hypothalamic Control of Biorhythms, Arousal, & Sleep

• Clock mechanisms cycle around the 24-hour period to regulate physiological mechanisms important for homeostatic functions.
• Biorhythms are entrained by the suprachiasmatic nucleus (SCN) from direct retinal inputs.
• The SCN is connected to other hypothalamic nuclei that regulate sleep/wake transitions.
• SCN lesions disrupt the 24-hr pattern of feeding, drinking, sleep, and overall activity. There are several brainstem circuits promote arousal by projecting to the thalamus, hypothalamus, basal ganglia and cerebral cortex.
• The ‘ascending arousal system’ is a more accepted term because some of the circuits involve areas of the reticular formation.
• Histamine neurotransmitter by neurons in the posterior half of the hypothalamus promote arousal.
• DM and TM nuclei synthesize histamine.
• Centrally active antihistamines promote drowsiness by inhibiting action of histamine neurons.
• Neurons of the POA hypothalamus are activated during the sleep cycle.
• Help switch from wakefulness to sleep with inhibitory control over the 'ascending arousal system'.
• POA neurons are influenced by basal forebrain cholinergic centers that respond to sleep-regulating chemicals.
• Neurons in middle (DM and lateral zone) and posterior hypothalamic levels use orexin (hypocretin) to activate the 'ascending arousal system'.
• A loss of these orexin neurons leads to narcolepsy (rapid transition when awake to sleep states).
• Orexin neurons can inhibit entry into REM sleep.

Hypothalamic Control of Reproduction and Maternal Behaviors

• Certain nuclei of the hypothalamus are sexually dimorphic, displaying size differences between males and females. Also exhibiting gender-specific expression of steroid/hormonal receptors.
• Subregions of the POA differ in size between males and females and have been associated with reproductive behaviors.
• The POA region is known to influence the release of reproductive hormones from the anterior pituitary gland. Subregions of the VM hypothalamus contain progesterone receptor-expressing cells related to mating.
• The POA is the center for maternal behaviors like nursing and infant care.
• Oxytocin increases onset of maternal behaviors and is linked to parent-child bonding.
• POA neurons do not likely sense oxytocin peripherally via posterior pituitary release.
  • Instead they have direct connections with oxytocin releasing neurons of the PVN, which project to the POA.
• Dopamine is a modulating neurotransmitter that is released in the POA and facilitate the effects of PVN oxytocin.

Hypothalamic Involvement in Memory

• It is known that hippocampal projections to the mammillary bodies provide a circuit for the formation of new declarative memories.
• The mammillary bodies receive virtually no intrahypothalamic connections and are separate from the rest of the hypothalamus that are vastly interconnected.
• Hypothalamic lesions produce memory deficits because of damage to the fornix, mammillary bodies, and/or mammillothalamic tracts.
• One could argue that the mammillary bodies are a separate entity with closer ties to limbic function and less functionally part of the hypothalamus.

Hypothalamic Control of Aggressive Behaviors

• Ranson elicited autonomic responses from anesthetized rats via stimulating discrete regions of the hypothalamus.
• Hess repeated in awake rats and observed responses plus complex behaviors like fear and rage.
• Cannon-Bard demonstrated 'sham-rage' by disconnecting cortex from the hypothalamus in cats.
• Cuts below the hypothalamus eliminates rage behavior.
• These studies indicate a neural axis involving limbic cortex-hypothalamus-brainstem for emotional behaviors linked with autonomic function.

Regional Division

Rostromedial parts

• Feelings of contentment
• Central control of the PANS.
• Stimulation of this region promotes passivity, satiety, decreased body temperature. Caudolateral parts
• Associated with feelings of anxiety.
• Stimulation increases SANS output, increased body temperature, and aggressive behavior.
• Contains the feeding center.