Physiology 1.04 - Neurophysiology-Subcortical System

PHYSIOLOGY

1.04 JULY 9, 2013

Neurophysiology - Subcortical Functions Munarriz, M.D.

Brainstem Modulatory Systems  control behaviors that require the coordination of many brain areas o [cerebral cortex and reticular activating system (RAS)] Consciousness (sleep/wake cycles) o Cognitive (learning and memory) o Attention and arousal o Motivation and reward (also, addiction) o Motor (movements)  involves FOUR neurotransmitter systems 1. noradrenergic 2. serotonergic 3. dopaminergic 4. cholinergic [1] Norepinephrine/Noradrenergic System  ↑ ATTENTION, ↑COGNITIVE WORK Norepinephrine  NE → Epi o Both degraded by MAO and COMT  released by locus ceruleus (in pons) > stimulates neocortex, cerebral cortex via NE receptors on cerebral neurons o β receptors – excitatory on postsynaptic neurons via AC o α1 receptors – excitatory on postSN via PKC o α2 receptors – inhibitory on postSN via AC  Sensory stimuli > locus ceruleus > increase in NE  Effects of increase in NE

 Cerebral Cortex: o ↑ ATTENTION, ↑COGNITIVE WORK  Amygdala: o Emotional response o Mood: emotionall response over a number of days  Hypothalamus, pituitary, adrenal axis: Increase in CRH (corticotropin releasing hormone) ↓ Increase in ACTH in anterior pituitary gland ↓ Increase in cortisol levels ↓

Increase in glucose levels for the consumption of the brain ↓ Increase mental activity  Basal ganglia and cerebellum: o increase accuracy of motor movements; seen more in athletes  Lower brainstem and spinal cord: o pain modulation →-less pain stimuli entering the brain → decreased suffering o VNC → vasoconstriction of blood vessels Levels of NE  ↓↓↓ levels - anxiety, depression, decreased attention, irritability, increased frustration  ↑↑↑ levels (for a long period of time) - mania (prolonged exuberance) [2] Serotonergic System  MOOD STABILITY Serotonin (5TH)  released by dorsal raphe nucleus  from tryptophan → degraded by tryptophan hydrolase and AA decarboxylase → 5HT → degraded by MAO → 5HIAA  ↑ NE → ↑5TH o increase 5TH: mood stability o decrease 5TH: dec mood stability, may bring about mania

(PFC – Prefrontal cortex, SCN – suprachiasmatic nuclei, HPA – Hypothalamic-pituitary-adrenal, BG – basal ganglia, SN – septal nuclei(??)) Increased levels:  decreases sympathetic response to stress  Increase in memory and cognitive work  Decrease HPA stress response  More purposeful movements  [Brainstem] sleep cycles  Pain modulation Decreased levels:  anxiety, depression, irritability

TRANSCRIBERS: Eunika, Eli, Kenan, Catie, Von, Maja, Rissa, Trisha

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PHYSIOLOGY

Subcortical Functions

Euthymic State & Anxiety

Anxiety  imbalance between NE and 5HT  Amygdala is NOT stable  ↑ CRF from the hypothalamus → ↑↑↑ NE that is NOT opposed by (↓) 5HT → ↑↑↑ amygdala stress response  ↓ 5HT is the real reason for anxiety How to increase serotonin levels:  NOT meds (will make you very sleepy, ++++ sleepy)  chocolates – activates (BNST – bed nuclei of stria terminalis, CRF – corticotropin releasing factor, HIPP – hippocampus, LC – locus ceruleus, RN – raphe nuclei) Amygdala  gives emotion and consolidation  assesses the emotional significance of the events or outcome; grades your outcome Euthymic  a person who has learned how to confront his/her challenges effectively   Amygdala is stable o ↑ CRF from the hypothalamus → ↑ NE opposed by adequate amounts of (↑) 5HT → ↓ amygdala stress response o Inhibit dorsal PFC (to not be too stressful on the brain) o Stimulate ventral orbital PFC  Locus ceruleus o releasing NE at a stable or adequate level  Raphe nuclei o releasing 5HT at adequate level  increase 5HT levels to balance out NE Serotonin  for internally directed behavior  allows one to see whether one is handling situation well  e.g. comparing your grades for 1st shifting grade with 2nd shifting grade Norepinephrine  for externally directed behavior  allows one to see whether one is performing well  e.g. comparing grades with other people  tends to make us remember the negative memories while 5HT tends to decrease such memories "You should not be comparing yourself with others (because that will mean that you are increasing your norepinephrine). You should always be improving yourself. You know the standard. You know what you are trying to achieve. You know the level that you are trying to reach. And that is your main goal." –KDMunnariz, 2013

[3] Dopaminergic System  ↑ SENSE OF REWARD  goes hand in hand with serotonin system  mainly inhibitory  multiple subtypes (5) Tyrosine → DOPA MAO → Homovanillic Acid (HVA); COMT → DOPAC  2 areas where DOPA is released: VTA (ventral tegmental area) in midbrain and NA (nucleus accumbens) near septal nuclei in PFC VTA → septal nuclei, limbic cortex, amygdala → Medial Forebrain Bundle (MFB) → NA

(DA – dopamine, NA – nucleus accumbens, SN – septal nuclei) Functions:  motor control via substantia nigra  modulate short term memory, from VTA to PFC  reinforce behavior  takes part in “reward system”  Hypothalamus: endocrine response (prolactin), regulation of pituitary function  Substantia Nigra: ↑ initiation of motor movements Increased levels:  ↑ sense of reward (motivation)  Pleasure, euphoria  Motor function (fine tuning)  Compulsion, perseveration  fulfilled and satisfied – Hippocampus will keep the memories of reward through the help of serotonin Decreased levels: depression

TRANSCRIBERS: Eunika, Eli, Kenan, Catie, Von, Maja, Rissa, Trisha

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PHYSIOLOGY

Subcortical Functions

Drugs of abuse  acting upon NA and VTA  increase dopamine levels  gives pleasure, euphoria and compulsions [4] Cholinergic System  Acetyl CoA + Choline → CHAT → Ach → Achase  Basal forebrain: SN (septal nuclei) → neocortex and hippocampus (so that you are kept awake); DBB (diagonal band of Broca); laterodorsal tegmentum / PPT (pedunculopontine tegmentum) Functions:  Memory consolidation  Cognitive functions  ↓ levels → ↓memory

RETICULAR FORMATION 1. Consciousness - RF → sensory signals reach cerebrum → alertness 2. Somatic Motor Control - Pontine Reticulospinal Formation (excitatory)→ maintains tone of extensors - Medullary Reticular Formation (inhibitory)

Mechanisms that lead to consciousness: - Continuous transmission of signals from excitatory brainstem RAS to thalamo-cortical areas Mechanisms of decreased LOC (Level of Consciousness):** - stimulation of OR injury to RAS or to the bilateral cerebral hemispheres Clinical causes of Loss of Consciousness: - metabolic, toxic, CNS, etc. Arousal states: Alert → Lethargic → something → something → coma SLEEP-WAKE CYCLE - Two Process Model [1] Homeostatic sleep drive Increased duration of wake state ↓ Accumulation of serotonin and adenosine ↓ Sleep [2] Circadian alerting signal - influenced by Suprachiasmatic Nucleus (SCN) Dusk appears (darkness) ↓ ↓ light to retinal ganglion cells ↓ ↓ transmission of light signals passing through retinohypothalamic tract ↓ SCN stimulation ↓ Release of Melatonin from pineal gland ↓ ↑ Melatonin ↓ Inhibition of RAS ↓ ↓ alertness ↓ Sleep

3. Pain Modulation - RF → block transmission of pain at SC (spinal cord) - NE from LC and 5TH from Raphe Nuclei descends to the spinal cord to decrease transmission of pain impulses coming from the periphery 4. Mediates Autonomic Functions - Medullary cardiovascular (cardio-acceleratory center, cardio-inhibitory center, vasomotor center) - Respiratory control

Reticular Activating System - forward impulses to thalamocerebral hemisphere → alertness 4 Neurotransmitter systems Source NT Main effect LC NE ↑ attention, ↑ cognitive work RN 5HT Mood stability VTA DOPA ↑ sense of reward LDT/PPT Ach Memory consolidation Sensory impulses from: - visual - trigeminal - auditory - vestibular - tactile - proprioceptic from the limbs - visceral (nucleus tractus solitarius)

Activation of Excitatory RAS → Activation of thalamocortex (bilateral) → WAKEFULNESS Areas that keep us awake: 1. Sensory stimuli to Brainstem - all the neurotransmitters that is linked to the RAS - Ach (LDT/PPT), 5HT (RN), NE (LC), DA (VTA) 2. Hypothalamus  Orexin - released by Lateral Hypothalamus (LH) - stimulus for release: ↑ energy expenditure - ↑ food craving / become hungry -- ↑ food intake - Lesion in LH: obese individual – no food craving, no energy expenditure  Tubero Mamillary Nucleus (TMN) - TMN → release histamine → BF → awake - anti-histamine drugs will make you sleepy

CONSCIOUSNESS - Cortical and RAS activation 3. Thalamo-cortex - awareness of one’s self and environment - Basal forebrain → Ach - must be intact: brainstem RAS and bilateral cerebral hemispheres TRANSCRIBERS: Eunika, Eli, Kenan, Catie, Von, Maja, Rissa, Trisha

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PHYSIOLOGY

Subcortical Functions

Inhibition of excitatory RAS → Inhibition of thalamocortex (bilateral) → SLEEP Area that will cause you to sleep: 1. VLPO (VentroLateral PreOptic nucleus) VLPO → GABA → inhibit RAS → sleep 2. Pontomedullary raphe nuclei (PMRN) Pontomedullary nuclei → inhibitory serotonin** and adenosine (causes of fatigue of neurons) → decrease thalamo-cortex activity → sleep **Pontomedullary raphe nuclei releases INHIBITORY (→sleepy) serotonin while the dorsal raphe nuclei (of the four neurotransmitter systems) releases EXCITATORY (→awake) serotonin. Tips from Doc Munnariz: “SUREBALL” method to increase serotonin levels:  Meditation (5-10 mins, morning + evening)  Remove negative thoughts  Fill the brain with positive things REM sleep Promotion of Rapid Eye Movement (REM) sleep: 1. PMRN – promotes sleep 2. LDT/PPT – keeps you awake 3. LC – keeps you awake Why is LDT/PPT and LC active during REM sleep? During REM sleep, you are dreaming. Those dreams will allow you to see things and to understand what is going on in the dream so you need the Ach (from LDT/PPT) and the NE (from LC). For instance, if you are running in the dream, you need NE.

Stages of Sleep - N1, N2, N3 - Stage 1 → N1  Alpha to theta waves  Transitional state  Drowsy to restful sleep  Slow decrease in conscious awareness but still conscious about falling asleep - Stage 2 → N2  Theta; sleep spindles (EEG tracings wherein the person is already unresponsive to stimuli)  Zero conscious awareness  ↓ HR, RR, BP, temp - Stage 3 and 4 → N3  Delta waves; slow wave deep sleep  Parasomnias: sleepwalk, sleeptalk, night terrors - REM sleep  Paradoxical; 25% of total sleep time  rapid low-voltage high-frequency EEG desynchronization (beta, theta)  You feel awake but you are not  Despite ↓ tone → REM, myoclonic twitches, sudden movements  Cortical activation  ↓ PVR, CO, BP; ↓↑ HR, RR  Memorable dreaming - Narcolepsy  Always in N2 stage  Switch from α to theta waves LIMBIC SYSTEM - Found in both man and monkeys causing similar expressions (remember Bush and Teddy monkey!)

Beta waves are observed during REM sleep. Brain waves - From the most alert state to coma, occurs every 15 minutes: - β waves:  13-15 up to 30 Hz  Alert wakefulness - α waves:  8-13 Hz  transitioning from awake to sleep state  drowsy period - theta waves:  3-8 Hz; during stage 2 sleep  Related with memory, meditative (emotions and activity in the limbic system)  Light sleep - delta waves:  1-3 Hz  Slow-wave sleep; coma  Very deep sleep - Flat line:  Brain dead

Papez Circuit of the Limbic System All sensory stimulation → thalamus → PFC (decisions, goals, moral standards) → cingulate cortex (shift from one idea to another) → hippocampus (recording, assessment, memory consolidation) → amygdala (grading of the salience or significance of each emotional event) → basal ganglia (gives you your facial expression) → hypothalamus (SNS and PNS effects) → back to thalamus

TRANSCRIBERS: Eunika, Eli, Kenan, Catie, Von, Maja, Rissa, Trisha

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PHYSIOLOGY

Subcortical Functions

Thalamus  3 part: sensory, motor, limbic lobe ( a lot larger than the rest) Medial Auditory consolidation to areas Geniculate body 41 and 42 Lateral Visual consolidation geniculate body Ventroposterola Movement Sends output teral (VPL) from limbs to nucleus L – Lateral, somatosensory Limbs cortex (areas Ventroposterom Input from face 3, 1, 2) edial (VPM) M – Medial, nucleus Mukha *Anterior Part of limbic lobe; inputs coming from mamillary body (inputs thalamic nucleus from memory) → output to **cingulate cortex (shifting of attention from idea to idea, see options) Mediodorsal Inputs from PFC; short term nucleus memory; enables one to shift attention, plan, organize, multitask

Hypothalamus - Has autonomic nuclei, cardiovascular nuclei, endocrine nuclei, etc - Control centers of hypothalamus: (from Guyton)

SITUATION: Passing the final exams of the year. WE HAVE TO PASS.

Thalamus will relay audio-visual stimuli to the PFC. PFC will allow you to assimilate your material for *All memory stores will therefore go to your AT. Even studying. PFC also ha has the goal to make you pass. memory stores from the hippocampus goes to AT. Cingulate cortex will shift ideas (study now or study *Function of anterior thalamus region- cognitive later), hippocampus consolidating all material, all flexibility (You dealing with everything from memory) **Leaders of concept map making should have a good memories. If the amygdala is positive, (Kaya ko ‘to!) it cingulate cortex to enable shifting attention from an will accept the challenges more readily, unlike in idea of a classmate to the idea of another classmate, negative people (Di ko kaya, baka di to para sakin. thereby giving him ability to see options, helping him to /wrist). Positive people have NE and 5HT in adequeate go with the flow of events and a good PFC to direct the amounts while negative people have high NE but group to the final output. minimal 5HT (↑↑ NE:5HT ratio) → anxiety, agitation, tachycardia, all SNS responses. The response of basal Lesions of thalamic nuclei: - Cause the loss of a corresponding cortical area ganglia will be the facial expressions. because the thalamic nuclei are relay nuclei - Information passing through will disappear and not From 1D 2016 Trans: (galing daw it okay Dr. Munarriz) be transmitted The entire limbic system can be summarized to have Lesion/Problem on cingulate cortex: one function: MMOVE - End up with OCD features, less flexible thinking  M-emory (mammillary body and hippocampus - Will not allow you to shift from idea to idea are involved) and - Obsessive (fixated, stuck on thoughts, holds on to  M-otivation (comes from a sense of reward hurts of the past) and from the amygdala) - Argumentative (they are always right and no one  O- lfaction else is)  V- isceral (due to the hypothalamus)  E- motion Amygdala - Inputs come from all sesnse, including olfactory - Processes all sensory stimuli before going to context - The structure that responses to stress  Increase of NE in SNS  Increase in CRH through endocrine system - Via hypothalamus → effect on other brain areas  Lesion → abnormal placidity → on the peaceful side (Lesion of amygdala of every human → world peace. HAHAHA) - Has effects on PSNS (defecation, urination in response to stress) - Has responses in respiration, NE, DA and Ach systems → increased vigilance TRANSCRIBERS: Eunika, Eli, Kenan, Catie, Von, Maja, Rissa, Trisha

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