Central Nervous System
RETICULAR FORMATION
Brainstem contains a number of ill-defined, non-specific network of nerve cells and nerve fibers which constitute the reticular formation. It contains both descending and ascending pathways.
Connections to reticular formation are formed from cerebral cortex, basal ganglia, cerebellum, thalamus and hypothalamus. The ascending specific sensory tracts before ending in thalamic nuclei give off collaterals to the brain stem reticular formation.
ARAS (ascending reticular activating system)
Reticular formation sends diffuse nonspecific projections to cortex directly and also through intralaminar nuclei (Fig. 4.70). This ascending nonspecific pathway is called ARAS, as it is responsible for the cortical activity, leading to arousal and alertness. The EEG waves become desynchronised fast activity giving β waves. The activity of ARAS to cortex depends upon the sensory input, through collaterals from ascen-ding sensory tracts. Decrease in the activity of ARAS as a result of decreased sensory stimuli causes sleep, with EEG showing delta waves. The arousal reaction caused by the activity of ARAS, gives background activity in the cortex, for proper
appreciation of sensory stimuli which are projected to it. The awareness of sensory stimuli, environment and formation of thought processes leads to consciousness. The ARAS activity is believed to be responsible for these functions. The secondary response of evoked potentials is due to the ARAS activity. The arousal state is enhan-ced by epinephrine or sympathetic stimulation, which increases the ARAS activity. The actions of anesthesia, tranquilizers are mediated through the suppression of ARAS activity.
Descending reticulospinal pathway
The reticular formation in the medullary region receives inhibitory fibers from cerebral cortex caudate nucleus and anterior lobe of cerebellum (Fig. 4.61). The pontine reticular formation receives facilitatory influence from cortex. The activity of descending reticular formation depends upon the balance of activity between facilitatory and inhibitory regions of reticular formation. The descending reticulospinal tract influences γ motor neuron supplying the muscle spindles and maintains muscle tone. If facilitatory pontine reticular formation activity is unopposed, there will be increased firing of γ motor neurons resulting in rigidity.
If pontine reticular formation is suppressed or damaged, the muscle tone will be lost and posture cannot be maintained.
Fig. 4.70: Ascending reticular activating system (ARAS)
Functions of reticular formation
• Reticulospinal tract maintains muscle tone through its influence on γ motor neurons.
• The activity of ARAS gives rise to arousal and alertness. It is also responsible for sleep-wake cycle. Damage to the reticular activating system results in loss of consciousness (coma).
• Medullary reticular formation contains nerve cells, which are centers for regulating the activity of visceral organs such as heart, lungs, blood vessels, etc. Damage to medullary reticular formation suppresses the activity of these vital centers and results in death.
ELECTROENCEPHALOGRAM (EEG)
The thalamocortical nonspecific projections end on dendrites of cortical neurons and produce local hypo or hyperpolarizations, depending upon the type of transmitters released at the synapses. This electrical activity at the dendrites of cortical neurons causes current sink as the current goes in and out of dendrites (Fig. 4.71). These local, nonpropagatory synaptic potentials of dendrites of cortical neurons give oscillations or waves and can be recorded from the surface of the scalp.
These waves are known as electroencephalogram.
The current sink developed from dendrites leads to the formation of all or none law obeying propagatory action potential from the axon.
EEG recording can be done either by using bipolar or unipolar electrodes. The amplitude of the waves ranges from 5 μv to 100 μv.
Recording of EEG includes four types of waves.
Alpha wave
It has a frequency of 8 to 13/sec and amplitude ranges from 50 μv to 100 μv. It is a synchronized
wave recorded from a quite brain without any mental activity with the eyes closed. It is present more in the parieto occipital cortex. Alpha wave rhythm can be recorded, if the eyes are closed.
The alpha rhythm is also known as Berger rhythm. The alpha rhythm disappears when the eyes are open. The disappearance of alpha waves with the opening of eyes is called alpha block.
The alpha wave is replaced by fast activity desynchronized beta waves.
Beta wave
The frequency is 13 to 30 cycles/sec and the amplitude is 5 to 10 µv. It is a desynchronized fast activity wave produced during alertness or arousal state.
Theta wave
It is usually seen during light sleep and not when awake. Its frequency is 4 to 7/sec. The amplitude is recorded upto 10 µv. The presence of theta wave in EEG recording of adults when awake indicates brain tumors.
Delta wave
It is a slow wave with a frequency of 1 to 4/sec and amplitude reaches upto 100 μv. It is produced during deep sleep in adults. It is not seen in adults when awake. If produced, it indicates brain lesions. Delta wave is normally seen in newborn infants.
γγγγγ oscillations: They are recorded when an individual is aroused and focussed attention on some thing. Its amplitude ranges from 30 to 80 μv.
Uses of EEG
Clinically EEG recording is useful to localize pathological conditions like subdural hematoma, where the EEG activity is damped. EEG recording is also useful to identify epileptogenic foci in the brain. During epileptic seizures the EEG shows high voltage waves.
Fig. 4.71: Diagram to show how EEG waves are developed
The EEG wave is due to the dendritic activity. They are not the action potentials
SLEEP
Sleep-wake cycle follows circadian rhythm. In adults, the sleep period lasts for 6 to 7 hours and 16 to 18 hours in infants. The duration of sleep is gradually decreased during childhood. In old age, the duration is further reduced. During sleep, there is a temporary loss of consciousness with physiological changes, such as, fall in heart rate, blood pressure, respiratory rate and muscle tone.
There are two types of sleep which can be observed in an individual. They are slow wave sleep (SWS) and REM sleep (rapid eye movement sleep).
Slow wave sleep
It is a deep sleep and is interrupted 4 to 6 times in a day by REM sleep. SWS can be described with the help of EEG recording. There are four phases that can be noticed (Fig. 4.72).
I phase: The EEG shows fast activity beta waves (13 to 30 Hz) which are desynchronized. It indicates wakefulness.
II phase: The EEG shows synchronized alpha waves (8 to 13 Hz) as the person enters drowsiness.
III phase: The EEG records theta waves (4 to 7 Hz) and interspersed with spindles called sleep spindles. In this phase the individual enters light to moderate sleep.
IV phase: It is characterized by the presence of only slow waves delta (1 to 4 Hz). The sleep spindles disappear. The presence of delta wave during sleep indicates deep sleep state.
REM sleep
During every 80 to 90 minutes of SWS, the pattern of sleep changes. The deep sleep changes into light sleep, which leads to REM sleep lasting for a few minutes. This period gives rise to once again SWS. It can be seen that with successive REM periods, the interval between them is shortened and the duration of REM is increased (Fig. 4.73).
REM sleep is increased in infants, with a greater increase in premature infants.
Sleep disorders
• Insomnia: Lack of sleep. It occurs due to various medical and psychological conditions.
• Norcolepsy: It is the urge to go to sleep during day time. In this condition the REM sleep starts directly from light sleep with out going into deep sleep state.
REM sleep is characterized by rapid eye movements and it coincides with dream state. The EEG recording shows fast, desynchronized beta activity characteristic of arousal, eventhough, the threshold of awakening is increased. That is why, REM sleep is also called paradoxical sleep.
During REM sleep, the irregularities in cardiac action, arterial pressure, respiration can be noticed. It is during REM period, occasionally awakening occurs during sleep.
Genesis of SWS
There are three subcortical regions namely diencephalic sleep zone, medullary reticular formation and basal as basal forebrain sleep zone
Fig. 4.72: Recording of EEG during slow wave sleep Fig. 4.73: REM sleep periods in an adult
involved in the slow wave sleep. Recent studies have shown that serotonin agonists suppress sleep and its antagonists increases slow wave sleep in humans.
Genesis of REM sleep
The center of REM sleep is situated in the pontine reticular formation. The ponto-geniculo-occipi-tal spikes (PGO) develop due to cholinergic neuron activity, which causes REM sleep.
REM sleep is now considered significant in human beings for memory consolidation.
HYPOTHALAMUS
It is present in diencephalon and includes a number of nuclei. They are closely linked to limbic system, brainstem, cortex, and pituitary gland by their connections. These connections help the hypothalamus to control visceral, autonomic, endocrine and emotional responses. Hypo-thalamic neuronal activity gives appropriate behavioral responses to visceral and somatic sensory stimuli. The normal homeostasis in an organism depends upon the control of visceral and somatic functions, which are integrated in the hypothalamus.
Nuclei of hypothalamus
The nuclei can be included under four groups namely, periventricular, medial, lateral and posterior (Fig. 4.74).
The periventricular group includes the following nuclei:
Anterior Arcuate
Median eminence Suprachiasmatic Supra optic Para ventricular Medial group contains Dorso medial
Ventro medial Medial preoptic
Lateral group includes Lateral preoptic
Lateral hypothalamus Posterior group contains Posterior nucleus
Mamillary body
Connections of hypothalamic nuclei Afferent connections
Fornix connects hippocampus of limbic system to mamillary body.
Stria terminalis connects amygdala to lateral hypothalamus and preoptic area.
Medial forebrain bundle links septum to various hypothalamic nuclei.
Pallidothalamic fiber connects basal ganglia (lenticular nucleus) to the hypothalamus.
Noradrenergic bundle from locus ceruleus in the brainstem projects to the hypothalamus.
Serotonergic projections from Raphe nucleus go to the hypothalamus.
Efferent connections Mamillo thalamic tract Mamillo tegmental tract
Medial forebrain bundle from hypothalamus to the brainstem
Fig. 4.74: Hypothalamic nuclei
Tuberoinfundibular tract Hypothalamo hypophysial tract Functions of hypothalamus
The major functions of hypothalamus are in the regulation of visceral functions, behavior, and emotion. They are achieved by the hypothalamic control of autonomic nervous system, endocrine glands, somatic and motor functions.
Control of autonomic nervous system
Hypothalamus has a number of areas where electrical stimulation causes effects of sympa-thetic stimulation which is part of fear and rage reaction. Electrical stimulation of lateral hypo-thalamus, and posterior hypothalamus results in increased heart rate, increase in arterial blood pressure, pupillary dilatation, piloerection, etc.
They are the effects of sympathetic stimulation and from these studies, these areas are considered for controlling sympathetic activity.
Electrical stimulation of anterior hypothalamus gives parasympathetic responses, such as, salivation, fall in heart rate, fall in blood pressure, increase in GI secretion and motility, micturition, etc. These effects are due to the activity of parasym-pathetic nervous system and this area has been considered for controlling parasympathetic activity. The autonomic responses mentioned above are necessary for the regulation of visceral function and maintenance of homeostasis.
Temperature regulation
Hypothalamus acts as a thermostat, regulating the body temperature. The anterior hypothalamus responds to the rise in body temperature. Lesion of this region causes hyperthermia and absence of cutaneous dilatation and sweating when body temperature rises. Anterior hypothalamus acts as heat loss center.
The posterior hypothalamus is stimulated by fall in body temperature (hypothermia). It causes cutaneous vasoconstriction, piloerection (goose bumps in humans) and shivering. These effects help to reduce the heat loss and increase heat production (shivering). If cold exposure is
continued for a long time, thyroid and adrenal medulla are stimulated, as their secretion causes calorigenic action. The posterior hypothalamus is considered as heat gain center. The normal body temperature is due to the balance of activity between the heat loss and heat gain centers.
Regulation of food intake
Ventromedial nucleus of hypothalamus, when stimulated, causes stoppage of eating, while, the lesion of the same nucleus results in voracious eating (hyperphagia) leading to obesity. The ventromedial nucleus is the satiety center. The lateral hypothalamic nucleus is considered as feeding center. Electrical stimulation of this area causes increased appetite and feeding. Normal feeding depends upon the balance in the activity of satiety and feeding centers. The satiety center is tonically active as the glucoreceptors present around this nucleus show entry of glucose into it. The activity of VMN results in inhibition of feeding center. The satiety center is also influen-ced by distention of stomach and release of GI hormones like CCK, GRP, Somatostatin and glucagon.
The food intake regulation has also been explained by mechanisms, which include the suppression of appetite, and decreased food intake by the release of hormone leptin from adipose tissue, whenever fat deposition is increased. Leptin acts on the hypothalamus and decreases food intake by decreasing the activity of neuropeptide Y. The hormone neuropeptide Y when released causes increased food intake.
Regulation of body weight
Whenever the inhibition of satiety center occurs, it leads to increased food intake. The body weight increases and the satiety center is now reset for this increased body weight. After the attainment of increased body weight, the satiety center once again becomes active and inhibits the feeding center. This observation in animals led to the theory that VMN is responsible more for regulating the body weight, than regulating the feeding center.
Water balance
Lateral nuclei of hypothalamus, supraoptic nucleus, and regions around circumventricular organs near the third ventricle are considered centers for regulating water balance in the body.
Increase in osmolality of plasma, as in loss of water or infusion of hypertonic saline causes the activity of osmoreceptors located in anterior hypothalamus. The rise in tonicity of blood stimulates osmoreceptors and causes thirst. There is also secretion of vasopressin from suprotic and paraventricular nuclei, due to the shrinking of osmoreceptors. The vasopressin hormone causes reabsorption of water in the distal segment of nephron. The fall in body water would also cause a fall in blood volume. This stimulates renal renin- angiotensin system. The angiotensin II that is formed enters the hypothalamus and stimulates the thirst center situated in the subfornical organ and OVLT. This causes drinking behavior.
Control of anterior pituitary
Periventricular nucleus and arcuate nucleus send projections to median eminence as tubero infundibular tract. These neurons secrete various peptides and monoamines, which are either excitatory or inhibitory on anterior pituitary hormone secretion. These hormones are called hypothalamic releasing and inhibiting hormones.
From median eminence, they are transported to the anterior pituitary through hypophysial portal circulation. Some of the releasing hormones and their actions are as follows.
CRH- stimulates ACTH secretion
TRH- stimulates TSH,Growth hormone and prolactin secretion.
Somatostatin- inhibits growth hormone and TSH secretion.
GnRH- stimulates FSH and LH secretion.
Secretion of posterior pituitary hormones The supraoptic and paraventricular nuclear groups secrete vasopressin and oxytocin, which
are released from posterior pituitary. They are synthesized as large precursor molecule known as neurophysins I and II and transported along the axons of the hypothalamo-hypophysial tract to posterior pituitary.
Rage
Certain regions of hypothalamus like lateral hypothalamus and periventricular zone when stimulated show rage response. This aggressive behavior is due to hypothalamic connection with neocortex. If this connection is cut, the rage response can not be seen.
Sex behavior
Hypothalamus through its connection with the nuclei of limbic system, neocortex, endocrine glands and brainstem controls sex behavior. In humans, sex behavior is highly encephalized and hence the neocortex and association areas influence the sex behavior. In lower animals, oestrus, copulation are controlled by the hypo-thalamic nuclei, which include ventral and medial preoptic nuclei (Table 4.3).
Sleep
The diencephalic zone which includes posterior hypothalamus produces sleep when low frequency stimulation occurs. The basal forebrain sleep zone, which includes preoptic area is another region in the hypothalamus which also causes sleep by both low and high frequency stimulation. Damage to fibers coming from posterior hypothalamus results in sleep disorders.
Motivation
Medial forebrain bundle, which projects from limbic system to the brain stem through hypo-thalamic nuclei, is considered to be responsible for motivational behavior. It includes reward where the animal experiences pleasant effect when medial forebrain bundle or regions of hypothalamus and limbic system are stimulated electrically. The animal is motivated to press the
bar for self-stimulation. When the animal experiences unpleasant effect caused by the foot shock, it is taken as punishment and the animal learns to avoid it. This reward and punishment are considered as motivation for the animal.
Motivation is vital for the survival of the species.
Circadian rhythm
Suprachiasmatic nucleus is the center which controls circadian rhythm in the body such as secretion of adrenocortical hormones, body temperature, sleep-wake, etc. The input to the suprachiasmatic nucleus is the fiber coming from optic chiasma. The visual cues are essential for the diurnal rhythm.
Immunity
The hypothalamic regulation of sympathetic nervous system, adrenocortical and medullary secretions produce its effect on the immunity also.
It is commonly observed that chronic exposure to psychological stress, which activates hypo-thalamo-pituitary-adrenal axis, results in suppression of immunity. Lesions of hypothala-mic nuclei which are involved in the control of these functions, cause decreased immune response as evidenced by the reduced T cell lymphocytes in the blood.
Tabel 4.3: Regions involved and their functions in hypothalamus
No Functions Regions Involved
1 Regulation of body temperature Anterior hypothalamus (heat loss)Posterior hypotha-lamus (heat gain)
2 Regulation of autonomic nervous system Anterior hypothalamus – parasympathetic activity Posterior hypothalamus – sympathetic activity 3 Regulation of body weight by feeding and satiety Lateral nucleus – feeding Ventromedial nucleus – satiety 4 Regulation of plasma osmolality and ECF Anterior hypothalamus (osmoreceptors)
volume by thirst and secretion of ADH
5 Regulation of anterior pituitary hormone secretion Median eminence
6 Posterior pituitary gland secretion Supraoptic and paraventricular nuclei 7 Regulation of motivational behavior by reward Medial forebrain bundle
and punishment
8 Regulation of rage and sexual behavior Lateral hypothalamus (Rage)Anterior and ventral hypothalamus (Sexual behavior)
9 Control of sleep Preoptic (Basal forebrain sleep zone) Suprachiasmatic nucleus Diencephalic sleep zone (Posterior hypo-thalamus)
10 Control of body rhythm Suprachiasmatic nucleus