Hypothalamus

• Give overview of structure of hypothalamus

  Organised in nuclei with relatively shared functions, forms 2 small bilateral masses of grey matter below the thalamus, lie either side of and form the floor of the 3rd ventricle

  Wall of 3rd ventricle lined by ependymal cells, which are alpha and beta tanycytes - monitor the cerebral spinal fluid in the ventricle
• Give overview of functions of the hypothalamic nuclei

  PVN and supraoptic nuclei -water (ADH + oxytocin)

  Anterior nucleus - thermoregulation, parasympathetic stimulation

  Preoptic area - gonadotrophic hormone regulation

  SCN - circadian rhythms

  Dorsomedial nucleus - hunger

  Posterior nucleus - thermoregulation

  Lateral nucleus - hunger

  Mamillary body - fornix-thalamus

  Ventromedial nucleus - satiety

  Arcuate nucleus - DA neurons, hypothalamic releasing factors
• What are the 4 major connections of the hypothalamus?

  Medial forebrain bundle - Septal nuclei, olfactory regions <-> hypothalamus and brain stem

  Fornix - HC complex <-> mammillary bodies of hypothalamus

  Stria terminalis - amygdala <-> hypothalamus

  Mammillothalamic tract - hypothalamus <-> thalamus (anterior nucleus)
• What are the limbic functions of the dorsomedial, ventromedial, lateral, and mamillary nucleus

  Dorsomedial - emotional behaviour, stimulation causes obesity and savage behaviour

  Ventromedial - satiety centre, destruction causes obesity and savage behaviour

  Lateral - feeding centre, stimulation induces eating, destruction causes loss of appetite

  Mammillary - input from HC, lesions cause memory deficits
• Role of the mamillary bodies?

  Receive input from the HC via the fornix, project to the anterior nucleus of the thalamus through the mammillothalamic tract

  Lesions caused in Korsakoff syndrome - memory loss, confabulation, personality change associated - due to chronic alcohol use
• What are the autonomic connections of the hypothalamus?

  Dorsal longitudinal fasciculus:

  Hypothalamus <-> Brain stem reticular formation

  Hypothalamus <-> Brain stem nuclei, intermediolateral cell column

  Acts as head ganglion of the autonomic system to regulate almost all autonomic functions - body temp, heart rate, blood pressure, bladder contraction, hunger
• Role of circadian rhythms in endocrine rhythms?

  SCN = circadian pacemaker, info from melanopsin expressing retinal ganglion cells - influences neurosecretion and autonomic control via the SCN (extends to PVN, influences autonomic glutamate control of the upper thoracic spinal cord, preganglionic sympathetic projects to superior cervical ganglion, postganglionic sympathetic projects to the pineal gland to control the secretion of melatonin

  Inhibitory communication in dark from the PVN to stimulate melatonin secretion, stimulatory in the light to inhibit secretion
• Which nuclei are each of the hypothalamic releasing hormones secreted from?

  GnRH - anterior hypothalamus, preoptic nucleus

  TRF - Anterior and posterior hypothalamus

  DA - arcuate nucleus

  OX-VP - paraventricular nucleus, supraoptic nucleus
• What are the endocrine connections of the hypothalamus?

  Hypothalamo-Hypophyseal tract - Hypothalamus to the posterior pituitary

  Tuberoinfundibular tract - Arcuate nucleus to the median eminence
• Describe the organisation of the median eminence

  Difficult to visualise, normally study using immunocytochemistry

  Cell bodies in specific nuclei extend their axons to the median eminence and make contact with the capillaries, so when depolarised they secrete hormones into the blood

  Tanycytes are glial cells, extend long processes to the median eminence, sense nutrients in the cerebral spinal fluid, secrete local factors to affect the median eminence

  Vascular median eminence remodels during different homeostatic states (e.g pregnancy, lactation) to ensure efficiency of the hormones secreted
• Clinical evidence for feedback on hypothalamus

  TRH stimulation test humans, measured serum TSH using radioimmunoassay at different times

  Normal - increase in TSH after stimulation over 30 mins, decreases over next 30 mins back to baseline

  Primary hypothyroidism - very high levels of TSH before stimulation, increased rapidly over 15 mins after stimulation, decreased back to their raised baseline by an hour

  Hypothalamic hypothyroidism - same baseline as normal people, stimulation caused increase over 60 min, no decrease

  Hyperthyroidism - no change from baseline (full negative feedback)
• Changes in GnRH at puberty?

  Much higher frequency of pulses of GnRH release during puberty than in children (pulses ~every 90min), means pulses of FSH and LH follow

  Pulse generator of GnRH likely to be activated by kisspeptin, controls transition of behaviour of GnRH neurons - KO and mutation studies - KO means no sexual maturity, sex tissues (ovaries etc) atrophy

  Deletion kisspeptin gene meant mice infertile

  Kisspeptin release based on oestradiol, progesterone, and circadian inputs
• Effect of anterior pituitary tumours?

  Mechanical - presses on optic chiasm, affects vision (corrected if tumour removed)

  Hormonal - depends on cell type, by hypersecretion of a hormone

  Tumour removed using endoscopic reach via the nasal cavity
• Role of the hypothalamus in water homeostasis

  Increased blood osmolarity causes osmosensitive neurons to shrink, TRPV1 channels open, OVLT neurons depolarise and fire, make monosynaptic glutamatergic contacts with supraoptic nuclei neurons, so promotes firing ADH neurons and ADH release

  ADH neurons also intrinsically osmosensitive

  Increases water reabsorption in the kidney to return blood osmolarity to normal

  Diabetes insipidus due to disorders in ADH function - can be hypothalamic (lack of production) or nephrogenic (lack of response) - produce lots of very dilute urine
• How is thermoregulation influenced by the hypothalamus?

  Anterior hypothalamus - lesions cause hyperthermia - contains endogenous temperature sensitive neurons, T set-point can be changed by pyrogens, causes an elevated core temperature

  Posterior hypothalamus - lesions cause hypothermia - controls dilation or contraction of cutaneous circulation, and control of sweat glands
• Techniques other than lesions to study roles of neurons in hypothalamus?

  Optogenetics - depolarisation or hyperpolarisation of specific cells to due expression of opsin channels that were genetically encoded, respond to light

  DREADDS = designer receptors exclusively activated by designer drugs - virus containing the DNA injected into brain, CNO administered and binds to DREADD to selectively activate or inhibit the brain region
• What is Frolich syndrome?

  Caused by tumours of the hypothalamic area or their treatment

  Causes increased appetite and obesity, low FSH and LH, delayed onset of puberty, short stature, delayed growth, low body temperature, diabetes insipidus, somnolescence