NEUROENDOCRINOLOGY, KEY POSITION OF HYPOTHALAMUS Olga Vajnerová, 2nd Faculty of Medicine, Charles University, Prague, 2011

Ascending arousal system Frederic Bremer (30. years of 20. century) Cerveau isolé (intercollicular midbrain transection between colliculi superiores and inferiores) uncosciouness, EEG of sleep type Encephal isolé (transection at C1) Sleep and wakefulness alternate

Excitatory- activating system of the brain

Pyramidový neuron

Thalamocortical modulation

Neurohormonal control of brain activity The locus ceruleus and norepinephrine system Excitatory effects Modulatory effects (raise the excitability level of the cell and make it more likely to fire AP) REM sleep

Neurohormonal control of brain activity The substantia nigra and the dopamin Nigrostriatal system to caudate and putamen Either excitation or inhibition Destruction: Parkinson‘s disease

Neurohormonal control of brain activity The substantia nigra and the dopamin Ventral tegmental nucleus to the frontal lobe, ventral striatum, amygdala, other limbic structures Excessive activity: schizophrenia

Neurohormonal control of brain activity The raphe nuclei and the serotonin system Fibers to thalamus, cortex Descend to the spinal cord inhibitory Non REM sleep Supress pain

Hypothalamus, a major control headquarters for the limbic system

 Hypothalamus  Cortex  Thalamus  Temporal lobe  Basal ganglia  Septum  Paraolfactory area

Hypothalamus, a major control headquarters for the limbic system  Hypothalamus  Cortex  Thalamus  Temporal lobe  Basal ganglia  Septum  Paraolfactory area cingulate gyrus Parahippocampal gyrus Orbitofrontal cortex

Hypothalamus, a major control headquarters for the limbic system  Hypothalamus  Cortex  Thalamus  Temporal lobe  Basal ganglia  Septum  Paraolfactory area cingulate gyrus Parahippocampal gyrus Orbitofrontal cortex Anterior nuclei

Hypothalamus, a major control headquarters for the limbic system  Hypothalamus  Cortex  Thalamus  Temporal lobe  Basal ganglia  Septum  Paraolfactory area Cortex: cingulate gyrus Parahippocampal gyrus Orbitofrontal cortex Subcallosal gyrus Anterior nuclei Hippocampus Amygdala

Functions of hypothalamus

Connections: Caudally to the brain stem Rostrally to diencephalon limbic cortex Pituitary gland Hypothalamus controls: 1.Vegetative and endocrine functions 2.Behavior and motivation

Functions of hypothalamus

Olga Vajnerová using Mital Patel presentation Vegetative and endocrine functions

Hypothalamic hormones Adenohypophysis

Feed back regulation Kortizol Tyroxin

Hypothalamic hormones Neurohypophysis

QUESTION  PATIENT :  EXTREME THIRST  EXCESSIVE DILUTED URINATION DAY AND NIGHT  DEHYDRATION WHATS THE DIAGNOSIS?

QUESTION  PATIENT :  EXTREME THIRST  EXCESSIVE DILUTED URINATION DAY AND NIGHT  DEHYDRATION WHATS THE DIAGNOSIS? DIABETES INSIPIDUS ADH DEFICIENCY

Cardiovascular regulation Arterial pressure Heart rate Specific cardiovascular control centres are in…. Reticular regions of the pons and medulla Cardioexcitatory area Cardioinhibitory area Vasomotor area Via Sympathetic and Parasympathetic nerves Posterior and lateral hypothalamus increases Preoptic area decreases

Biological rhythms Suprachiasmaticus nuclei – retinohypothalamic tract Pacemaker of circadian rhythms Sleep – wake cycle ACTH secretion Melatonin secretion Body temperature rhythm Activity patterns of animals

Regulation of body water 1.Thirst center Lateral hypothalamus Osmoreceptors – when the EF is too concetrated – develops intense desire to drink water 2. Antidiuretic hormone

Gastrointestinal and feeding regulation Hunger center Lateral nuclei of the hypothalamus stimulation – extreme hunger, appetite, craving for food, hyperphagia Destruction of this area – lethal starvation, weight loss, muscle weakness, decreased metabolism Is permanently active Satiety center Ventromedial nuclei of the hypothalamus Stimulation – sense of complete satiety, refusal of food, aphagia Destruction – hunger centers overactive, continuing eating, obesity

Other important nuclei in feeding regulation Paraventricular, dorsomedial and arcuate nuclei of the hypothalamus ncl arcuatus = ncl infundibularis The site where multiple hormones converge to regulate food intake and energy expenditure Hypothalamus Receives hormonal signals (from GIT, adipose tissue) neural signals (from GIT) chemical signals (from blood about nutrients) signals from cerebral cortex (sight, smell and taste)

Feedback mechanisms for control of food intake Stretch receptors in the stomach PYY Cholecystokinin Insulin Leptin Supress futher feeding Ghrelin – during fasting Stimulates apetite

Short-term regulation of food intake - gastrointestnal filling - GIT hormonal factors – CCK, insulin, ghrelin - oral receptors meter food intake Oral factors related to feeding such as chewing, salivation, swallowing, tasting

Intermediate and long-term regulation of food intake - concentration of glucose, amino acids, and lipids glucostatic theory of hunger and feeding regulation (rise in blood glucose level increases firing of neurons in the satiety center, decrease in hunger center - Temperature regulation and food intake Cold increased feeding Interaction between temperature-regulating systém and food intake-regulating systém - Feedback signals from adipose tissue - leptin

Orexigenic substances stimulate feeding Ghrelin Anorexigenic substances inhibit feeding CCK, insulin, leptin, PYY

Regulation of body temperature Temperature regulating centers Temperature receptors

Regulation of body temperature Temperature regulating centers Temperature receptors 1. Peripheral Skin receptors (cold and warm) Deep body temperature receptors Spinal cord, abdominal viscera and great veins 2. Central Temperature detectors in hypothalamus Heat sensitive neurons, cold sensitiv neurons Praeoptic area

Posterior hypothalamus integrates the central and peripheral temperature sensory signals Control Heat-producing Heat- conserving reaction of the body Set point – crucial temperature level 37.1ºC Feedback gain for body temperature control

Temperature-decreasing mechanisms Vasodilation of skin blood vessels Inhibition of the sympathetic centers in the posterior hypothalamus Sweating Praeoptic area, via autonomic pathways to the spinal cord Sympathetic but cholinergic Decrease in heat production Inhibition of shivering and thermogenesis

Temperature-decreasing mechanisms Vasodilation of skin blood vessels Inhibition of the sympathetic centers in the posterior hypothalamus Sweating Praeoptic area, via autonomic pathways to the spinal cord Sympathetic but cholinergic Decrease in heat production Inhibition of shivering and thermogenesis

Temperature-decreasing mechanisms Vasodilation of skin blood vessels Inhibition of the sympathetic centers in the posterior hypothalamus Sweating Praeoptic area, via autonomic pathways to the spinal cord Sympathetic but cholinergic Decrease in heat production Inhibition of shivering and thermogenesis

What are temperature-increasing mechanisms ?? No Vasodilation of skin blood vessels NO Sweating Increase in heat production

Temperature-increasing mechanisms When the body is too cold 1. Vasoconstriction of skin blood vessels Stimulation of the sympathetic centers in the posterior hypothalamus 2. Piloerection via autonomic pathways to the spinal cord Sympathetic stimulation causes arrector pili muscles to contract 3. Increase in heat production, thermogenesis Shivering, sympathetic excitation of heat production, Thyroxin secretion

3. Increase in heat production, thermogenesis Shivering Primary motor center for shivering in the dorsomedial portion of the posterior hypothalamus Excited by cold signals from the skin and spinal cord Tr hypothalamoreticularis, hypothalamospinalis to spinal motoneurons Non rhytmical signals, increase the tone of the skeletal muscles Probably feedback oscillation of the muscle spindle stretch reflex Sympathetic excitation of heat production Chemical thermogenesis, E and NE uncouple oxidative phosphorylation, energy in the form of heat but do not cause ATP to be formed Thyroxin secretion

Sympathetic excitation of heat production Chemical thermogenesis, E and NE uncouple oxidative phosphorylation, energy in the form of heat but do not cause ATP to be formed Thyroxin secretion

Transmission of emotions from limbic system Rage, anxiety and fear, joy, sadness Is connected with visceromotor and somatomotor reaction Heart rate, breathig rate, vasomotor reaction – pale or red skin, sweat glands, gastrointestinal motility and secretion, smooth muscle in skin, shivering

Influence on respiratory and gastointestinal reflexes Olfactory stimulus – from paleocortex Signals to visceromotor centres in medulla – nausea, vomiting

Relation to autonomic function Parasympathetic responses Urinary bladder contraction Sympathetic responses Increased adrenal medullary secretion Vasoconstriction Stress – fight or flight