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Home , Second messenger system, Somatic nervous system

AUTONOMIC

assoc. prof. Edyta Mądry MD, PhD Department of Physiology Poznań University of Medical Sciences Basic Functions of the Nervous System

1. Sensation ▪ Monitors changes/events occurring in and outside the body. Such changes are known as stimuli and the cells that monitor them are receptors. 2. Integration ▪ The parallel processing and interpretation of sensory information to determine the appropriate response 3. Reaction ▪ Motor output. – The activation of muscles or glands (typically via the release of (NTs)) Nervous System’s Organization

◼ 2 big initial divisions: 1. ▪ The + the – The center of integration and control 2. Peripheral Nervous System ▪ The nervous system outside of the brain and spinal cord ▪ Consists of: – 31 Spinal ▪ Carry info to and from the spinal cord – 12 ▪ Carry info to and from the brain Peripheral Nervous System

◼ Responsible for communication btwn the CNS and the rest of the body. ◼ Can be divided into: Sensory Division =Afferent division – Conducts impulses from receptors to the CNS – Informs the CNS of the state of the body interior and exterior – Sensory fibers can be somatic (from skin, skeletal muscles or joints) or visceral (from organs) Motor Division=Efferent division – Conducts impulses from CNS to effectors (muscles/glands) – fibers Motor Efferent Division

◼ Can be divided further: – Somatic nervous system ▪ Somatic nerve fibers that conduct impulses from the CNS to skeletal muscles

– ▪ Conducts impulses from the CNS to , cardiac muscle, and glands. Autonomic Nervous System

◼ Can be divided into:

– Sympathetic Nervous System

– Parasympathetic Nervous System

These 2 systems are antagonistic. Typically, we balance these 2 to keep ourselves in a state of dynamic balance. Autonomic Nervous System

– Sympathetic Nervous System ▪ “Fight or Flight” – Parasympathetic Nervous System ▪ “Rest and Digest”

These 2 systems are antagonistic. Typically, we balance these 2 to keep ourselves in a state of dynamic balance.

Principal components of ANS

◼ Central components: hypothalamus, certain brain stem regions and nuclei, spinal cord

◼ Peripheral components: ganglia and nerves (both sensory and efferent ) Functional of ANS

◼ Sympathetic division of ANS – central neurons (preganglionic nerve cells) in the intermediolateral cell column of the spinal cord (Th1-12 i L1-3)

◼ Parasympathetic division of ANS - central neurons in the nuclei of cranial nerves: oculomotor (III), facial(VII), glossopharyngeal(IX), vagus(X) and in the intermediolateral cell column of the spinal cord (S2-4)

◼ (ENS) – neurons lying within the walls of the gastrointestinal system (control of motility, secretion and blood flow)

◼ adrenal medulla !!! Efferent pathways of ANS

(Th1-12 i L1-3) (III, VII, IX, X, S2-4) Autonomic Ganglionic transmision Autonomic and somatic efferent innervation Effectors of ANS

◼ smooth muscles ◼ heart ◼ glands ◼ nervous tissue ◼ adipose tissue Principal components of ANS

◼ Central components: hypothalamus, certain brain stem regions and nuclei, spinal cord

◼ Peripheral components: ganglia and nerves (both sensory and efferent neurons) Autonomic Nervous System:

◼ controls visceral functions

◼ conscious control – minimal (UNVOLUNTARY)

Somatic Nervous System:

◼ controls skeletal muscles

◼ under conscious control (VOLUNTARY) AUTONOMICAutonomic NervousNERVOUS System SYSTEM

◼ Function of ANS is reflex (see the end of presentation) and simple autonomic reflexes in the peripheral parts of ANS may occur within one organ AdrenalAdrenal medullamedulla

◼ Functionally related to the symathetic nervous system. ◼ It is regarded as a sympathetic ganglion in which the postganglionic neurons have lost their and become secretory cells ◼ After hypothalamic stimulation it releases catecholamines, which may affect autonomic adrenic receptors

Polygraphy

Lie detection, truth verification AutonomicAUTONOMICZNY Nervous UKŁAD System

◼ Techniques based on meditation allow, to a certain degree, consciously control AUN.

The relaxation response -  in oxygen consumption,  HR,  RR,  respiration rate RegulatoryRegulatory systemssystems of of ANS ANS

◼ - „cerebral cortex of the ANS” (cortically stored past experiences can be evoked by external stimuli (smells, sounds, sights).They can cause emotional reactions leading to strong visceral responses coordinated by ANS)

◼ Hypothalamus ◼ Solitary nucleus of the medulla – coordinates heart and respiratory functions ◼ Circulating catecholamines – affect adrenergic receptors GeneralGeneral characteristicscharacteristics ofof ANSANS

◼ usually dual and antagonistic innervation of the visceral organs

◼ ganglia in the efferent pathways

◼ large quantity of synapses in the ganglia

◼ cotransmitters and neuromodulators (they may coexist at most ganglionic synapses )

◼ postganglionic unmyelinated nerve fibers in the efferent pathways Comparison of efferent pathways SNS and PNS

Anatomical Pre- Post- Transmitter Transmitter localization ganglionic ganglionic (ganglia) (nerve fiber fibers fibers ends) Sympathetic Thoraco- Short Long ACh NE lumbar segments (Th1-12; L1- 3)

Para- Cranial and Long Short ACh ACh sympathetic sacral segments (III, VII, IX, X; S2-4) Different nerve endings in ANS

Discrete („precise”) synapses of Diffuse synapses of SNS activate PNS large surface area of one cell or large number of cells SNS – fight-or-flight respons

◼ in the emergency situations; mobilization of energy sources ◼ increase in heart rate and force; RR ◼ redistribution of blood from viscera to active skeletal muscles and heart ◼ inhibition of gastrointestinal activity ◼ ACTH secretion and secretion of catecholamines ◼ dilation of respiratory airways ◼ widening of pupil and accomodation for far vision ◼ „cold” sweating ◼ total activation !!! PNS – feeding and vegetative behavior “rest-and-digest”

◼ energy accumulation from food (intestinal digestion and absorption); waste products removal ◼ increases intestinal motility ◼ and defecation ◼ activated partially according to body demands !!!! ◼ dominates during the night Sympathetic Trunks and Pathways

A preganglionic fiber follows one of three pathways upon entering the paravertebral ganglia:

1. Synapses with the ganglionic within the same ganglion 2. Ascends or descends the sympathetic chain to synapse in another chain ganglion 3. Passes through the chain ganglion and emerges without synapsing Paradoxical fear

◼ PNS- normally dominates over sympathetic impulses

Paradoxical fear when there is no escape route or no way to win – causes massive activation of parasympathetic division – loss of control over urination and defecation

Acetylcholine

Choline acetyltransferase (ChAT) Acetylcholinesterase (AchE)

Acetyl-CoA Acetate + + Choline Choline metabolism

-NE may be recycled back into vesicles for later release (80%)

-NE they may be degraded by the : monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)

-NE may travel to the blood NON-adrenergic sympathetic fibers - examples

◼ Cholinergic: - sweat glands (except hands) - vascular smooth muscles in - salivary glands - vascular smooth muscles of penis (erection)

◼ Histaminic: - vascular smooth muscles of skeletal muscle, skin, brain Reflexes of ANS

Viscero-visceral Viscero-somatic Somato-visceral

From interoreceptors From internal organs From exteroreceptors – to internal organs to SNS to internal organs (effectors) e.g. reffered pain or e.g. acupuncture, e.g. micturition, muscular defense warm compresses defecation (convergention of the afferent pathways onto one spinal segment)

Referred Pain

Pain stimuli arising from the viscera are perceived as somatic in origin

- due to the fact that visceral pain afferents travel along the same pathways as somatic pain fibers Referred Pain Referred Pain Referred Pain

Dr n. med. Edyta Mądry Receptors for autonomic transmitters

◼Cholinergic: ◼Adrenergic: - nicotinic (N) - alpha  - muscarinic (M) - beta  Cholinergic nicotinic receptors( N)

◼ ionotropic receptors are ion channels to which neurotransmitters bind directly in order to open them. ◼ localization: - autonomic ganglia - adrenal medulla - motor end plate

◼ activation (via Ach) produces fEPSP of the ganglionic neurons ◼ The effect of ACh binding to nicotinic receptors is always stimulatory ◼ agonist - ◼ antagonist - atropine, hexamethonium (ANS), curare (motor end plate) Cholinergic muscarinic receptors

(M1-M8)

◼ Work via the second messenger system (IP3 and DAG) ◼ M1 – postsynaptic membranes; M2 – presynaptic membranes ◼ Agonist - muscarine ◼ Antagonist – - atropine,scopolamine M2), -pirenzepine (M1, M4) ◼ The effect of ACh binding: – Can be either inhibitory or excitatory – Depends on the type of the target organ

Receptor type M2 – inhibition of adenylate cyclase – outflux of K ions – membrane hyperpolarization

Amanita muscaria-source of muscarine Adrenergic receptors

◼ Alpha receptors – norepinephrine ◼ Beta receptors - epinephrine Adrenergic receptors 1

◼ Rec 1 - salivary glands, mucus glands of bronchi, muscles of: blood vessels, uterus, gastrointestinal tract ◼ They work via the second messenger system (IP3) ◼ Agonist – methoxamine, phenylephrine ◼ Antagonist – prazosin (1) and phentolamine (nonselective) AdrenergicAdrenergic receptorsreceptors  22

◼ Rec 2 – mainly in the presynaptic terminals - ; their activation controls the amount of neurotansmitter that is released (inhibition of reuptake-feedback inhibition) ◼ Inhibition of adenylate cyclase and inhibition of cAMP generation Agonist – clonidine Antagonist - yohimbine Adrenergic receptors 1 and 2

◼ 1 - heart, kidney, adipose tissue; 2 – smooth muscles of airways ◼ second messenger - cAMP ◼ Activation of presynaptic 2 receptors increases release of NE (feedback excitation) ◼ Agonist - phenoterol (2) ◼ Antagonist - propranolol (nonselective), metoprolol (1) Ganglionic transmission

Which of the autonomic receptors is most important in ganglionic transmission? Phase 1: ACh binds to N receptor on ganglionic cell causes depolarization (fEPSP); ACh binds to M1 receptor (SIF cells) causes release; Dopamine binds to D1 receptor causing K+ permeability and hyperpolarization (IPSP) Phase 2: ACh binds to M1 and M4 receptors causing K+ permeability and slow depolarization (sEPSP) Phase 3: (lsEPSP) Gn-RH as a neuromodulator causes slow depolarization The effects of ANS

1. Which system is responsible for stress response? 2. Describe the changes in fight-or- flight reaction Adrenergic and cholinergic stimulation Organ SNS PNS

Heart  rate and force  rate and force (β1) (M1) Bronchi dilation (β2) constriction (M3) mucus–inhibition (α1) mucus-increase (M1) Pupil dilation (α1) constriction (M1)

Adipose tissue  lipolysis (β3) no effect

Kidney  urine production  urine production (α1, β1) External male ejaculation (α1) erection (M1) reproductive organs Adrenergic and cholinergic stimulation Organ SNS PNS

Bladder relaxation of contraction of detrusor (β2, β3), detrusor (M2, M3), contraction of relaxation of internal sphincter(α) internal sphincter Rectum contraction of relaxation of internal sphincter, internal sphincter relaxation of contraction of smooth muscles smooth muscles Gastrointestinal  peristalsis (β2 )  peristalsis (M1) system and gastric juice and gastric juice production (α1, α2) production (M1) Salivary glands production of high  production of viscosity saliva (α1) watery saliva (M1) Disorders of the Autonomic Nervous System: Raynaud’s Disease

◼ Raynaud’s disease – characterized by constriction of blood vessels – Provoked by exposure to cold or by emotional stress Disorders of the Autonomic Nervous System: Hypertension ◼ Hypertension – high blood pressure – Can result from overactive sympathetic vasoconstriction Disorders of the Autonomic Nervous System: Achalasia of the Cardia ◼ Achalasia of the cardia – Defect in the autonomic innervation of the esophagus Quick repetition cAMP receptors:

ATP Adenylate cyclase cAMP

Protein kinase A

Cellular effects: e.g. increased influx of Ca++ in heart; activation of lipase in the adipose tissue → lipolysis Quick repetition cycle receptors: T+R+Gs+GTP

Phosphatidylinositol C Phosphatidylinositol biphosphate (PIP2) (PIP)

IP3 triphosphate - release of Ca++ from ER DG diacylglycerol kinase C - proton pump activation

- protein phosphorylation Quick repetition

Convertion of an extracellular event - the binding of a signal molecule – into an intracellular response that modifies the behavior of target cell

◼ Phase I – binding of first messenger (transmitter) to the receptor (T+R)

◼ Phase II – transduction of a signal into the intracellular compartment. T+R complex interacts with a specific G-protein; T+R+G complex binds GTP, which activates  subunit of

◼ Phase III – activated  subunit of G protein activates (or inhibits) a specific (eg. adenylate cyclase or ), which causes synthesis of second messenger Quick repetition

When a first messenger binds to a G-protein coupled receptor, the receptor changes its conformation and activates several G-protein  subunits. Each  subunit breaks away from the  complex, and activates a single effector protein, which in turn, generates many intracellular second -messenger molecules. One second messenger activates many enzymes, and each activated enzyme can regulate many target (amplification) Quick repetition

Action of Epinephrine

https://www.youtube.com/watch?v=ShBAvYDAV9I&index=6&list=PLXwnjgs_UWpIyKAZAction of Epinephrine 9yaEUbv8Sz1AMve45 Amplification Quick repetition

When a first messenger binds to a G-protein coupled receptor, the receptor changes its conformation and activates several G-protein  subunits. Each  subunit breaks away from the  complex, and activates a single effector protein, which in turn, generates many intracellular second -messenger molecules. One second messenger activates many enzymes, and each activated enzyme can regulate many target proteins (amplification) Quick repetition

Parasympathetic Responses

• Enhance “rest-and-digest” activities • Mechanisms that help conserve and restore body energy during times of rest • Normally dominate over sympathetic impulses • SLUDD type responses = salivation, lacrimation, urination, digestion & defecation and 3 “decreases”--- decreased HR, diameter of airways and diameter of pupil • Paradoxical fear when there is no escape route or no way to win – causes massive activation of parasympathetic division – loss of control over urination and defecation Quick repetition Quick repetition

Reflexes

• Reflex is a fast, involuntary, unplanned sequence of actions that occurs in response to a particular .

• Some reflexes are inborn ( pulling your hand away from a hot) • Other reflexes are learned or acquired.

63 Quick repetition

Reflex arc

• The pathway followed nerve impulses that produce a reflex is a . • A reflex arc includes the following five function components: – sensory receptor – sensory neuron – integrating center – – effector