Lecture Presentation by LeeAnn Frederick

Lecture Presentation by LeeAnn Frederick
University of Texas at Arlington Modified by James R. Jabbur Pauline P. Ward Houston Community College

An Introduction to the Autonomic Nervous System and Higher-Order Functions
Learning Outcomes 16-1 Compare the organization of the autonomic nervous system with that of the somatic nervous system. 16-2 Describe the structures and functions of the sympathetic division of the autonomic nervous system. 16-3 Describe the mechanisms of sympathetic neurotransmitter release and their effects on target organs and tissues.

Learning Outcomes 16-4 Describe the structures and functions of the parasympathetic division of the autonomic nervous system. 16-5 Describe the mechanisms of parasympathetic neurotransmitter release and their effects on target organs and tissues. 16-6 Discuss the functional significance of dual innervation and autonomic tone. 16-7 Describe the hierarchy of interacting levels of control in the autonomic nervous system, including the significance of visceral reflexes.

Learning Outcomes 16-8 Explain how memories are created, stored, and recalled, and distinguish among the levels of consciousness and unconsciousness. 16-9 Describe some of the ways in which the interactions of neurotransmitters influence brain function. Summarize the effects of aging on the nervous system and give examples of interactions between the nervous system and other organ systems.

16-1 An Introduction to the Autonomic Nervous System and Higher-Order Functions
Somatic Nervous System (SNS) Operates under conscious control (reflexes?*) Controls skeletal muscles Not homeostatic Autonomic Nervous System (ANS) Operates without conscious instruction (not aware) Controls visceral effectors (a.k.a. Visceral NS) Coordinates system functions that maintain homeostasis (i.e. cardiovascular, respiratory, digestive, urinary, reproductive)

OVERVIEW OF NEURAL INTEGRATION
CHAPTER 15 CHAPTER 16 Sensory processing centers in brain Higher-Order Functions Conscious and subconscious motor centers in brain Memory, learning, and intelligence may influence interpretation of sensory information and nature of motor activities Sensory pathways Motor pathways Somatic Nervous System (SNS) Autonomic Nervous System (ANS) General sensory receptors Skeletal muscles Visceral effectors (examples: smooth muscle, glands, cardiac muscle, adipocytes) 6

Comparing the Efferent Organization of the Somatic and Autonomic Nervous Systems

Divisions of the Autonomic Nervous System
The Autonomic Nervous System has 3 divisions The Sympathetic division increases alertness, metabolic rate, and muscular abilities It is applied under conditions of exertion, stress or emergency (fight or flight) The Parasympathetic division reduces metabolic rate and promotes digestion It is applied under conditions of normalcy (rest or digest) The Enteric division is an extensive network in the walls of the digestive tract that locally coordinates complex visceral reflexes (covered in Chapter 24)

Sometimes, the two divisions work independently
Most often, the sympathetic and parasympathetic divisions have opposing effects (physiologically) If the sympathetic division causes excitation, the parasympathetic causes inhibition Sometimes, the two divisions work independently This occurs when only one division innervates a particular structure The two divisions may also work together, with each controlling one stage of a complex process

16-2 The Sympathetic Division
Preganglionic neurons originate in the lateral gray horns between segments T1 and L2 of the spinal cord. That is why the Sympathetic Division is referred to as “thoracolumbar” These short preganglionic fibers ventrally exit the spinal cord and synapse in ganglia near the spinal cord, releasing Acetylcholine as a neurotransmitter Long postganglionic neurons (also called ganglionic fibers) originate in ganglia and terminate on target organs, releasing Norepinephrine as a neurotransmitter This division prepares the body for crisis, producing a “fight or flight” response

Sympathetic Responses
There are seven responses to increased Sympathetic activity (“fight or flight”) Heightened mental alertness Increased metabolic rate Activation of energy reserves Increased respiratory rate and respiratory passageway dilation Increased heart rate and blood pressure Activation of sweat glands Reduced digestive and urinary functions

Hold on to your seats, now it gets complicated
(…and that’s an understatement!)

Organization and Anatomy of Sympathetic Division
After exiting the spinal cord, each ventral root gives rise to a myelinated white ramus, which carries myelinated preganglionic fibers into a nearby sympathetic chain ganglion The presympathetic fibers then synapse on postganglionic fibers: within the sympathetic chain ganglia at the collateral ganglion or within the adrenal medullae

SYMPATHETIC (PARAVERTEBRAL) CHAIN GANGLIA
Spinal nerve Preganglionic neuron Autonomic ganglion of right sympathetic chain dorsal Autonomic ganglion of left sympathetic chain Innervates visceral/exterior effectors by spinal nerves White ramus ventral Sympathetic nerve (postganglionic fibers) Ganglionic neuron Gray ramus Innervates visceral organs in thoracic cavity by sympathetic nerves Are paired, laterally There are 2 innervation patterns with: Visceral organs in the thoracic cavity Visceral and Exterior effectors via spinal nerves Both innervation patterns occur on each side of the body KEY Preganglionic neurons (myelinated) Note: Both innervation patterns occur on each side of the body. Ganglionic neurons (unmyelinated)

COLLATERAL (PREVERTEBRAL) GANGLIA
dorsal Lateral gray horn Splanchnic nerve (preganglionic fibers) White ramus ventral Collateral ganglion Innervates visceral organs in abdominopelvic cavity Postganglionic fibers Are unpaired and located medio-ventrally 1 synaptic pattern innervates abdominopelvic tissues and organs They are composed of the celiac, superior and inferior mesenteric ganglion Each collateral ganglia is innervated by a branch of the splanchnic nerve

Secretes neurotransmitters into general circulation
THE ADRENAL (SUPRARENAL) MEDULLAE dorsal ventral Preganglionic fibers Adrenal medullae Secretes neurotransmitters into general circulation Endocrine cells (specialized ganglionic neurons) Are pseudo-paired, anterio-laterally Preganglionic fibers pass through the collateral ganglion to get to the interior of the adrenal medullae Medullary neuroendocrine cells possess very short axons (they are modified sympathetic nerves) When stimulated, they release epinephrine and norepinephrine into the bloodstream, having long lasting, systemic effects (Chapter 18)

Preganglionic fibers can extensively diverge; one preganglionic fiber can synapse on several postganglionic neurons (single “collateral ganglia”) In addition, preganglionic fibers can run between the sympathetic ganglia and interconnect them, making the chain look like a string of pearls (paired “chain ganglia”) There are approximately 26 sympathetic chain ganglion in the sympathetic chain; each ganglion innervates a particular body segment or group of segments These points are shown on the following schematic, as well as the distribution of sympathetic innervation

Sympathetic activation changes the activities of tissues and organs by:
Releasing Norepinephrine at peripheral synapses, which targets specific effectors, like smooth muscle fibers in the blood vessels of the skin (vasoconstriction shunts blood flow to skeletal muscles for physical action) It also distributes Epinephrine and Norepinephrine throughout the body in the bloodstream, causing the entire division to respond (sympathetic activation is controlled by sympathetic centers in hypothalamus, altering Central Nervous System activity – i.e. arousal, alertness, etc…)

Sympathetic Chain Ganglia
Sympathetic Summary KEY Preganglionic fibers Postganglionic fibers Hormones released into circulation Postganglionic neurons in the sympathetic chain and collateral ganglia exert their effects through innervation of peripheral target organs. Postganglionic Neurons Target Organs Sympathetic Chain Ganglia (paravertebral-paired connection) consists of a series of interconnected ganglia located on either side of the vertebral column. Visceral effectors in thoracic cavity, head, body wall, and limbs (increase heart and respiratory rates, blood flow, sweat,etc…) Preganglionic Neurons Lateral gray horns of spinal segments T1-L2 Sympatheitc “Thoracolumbar” Division Collateral ganglia (prevertebral- singular connection) are located ventrally within the abdominopelvic cavity. It includes the celiac, superior and inferior mesenteric ganglion. Sympathetic Chain Ganglia Visceral effectors in abdominopelvic cavity (stop digestion, release stored energy) Adrenal medullae (suprarenal medullae) is an endocrine organ that releases neurotransmitters Into the bloodstream Effects many organs and systems throughout the entire body! Postganglionic neurons in the adrenal medullae affect target organs throughout the body through the release of hormones into the general circulation. 20

16-3 Various Sympathetic Neurotransmitters
Axon terminals form branching networks of telodendria instead of synaptic terminals The telodendria form a chain of sympathetic varicosities, swollen segments packed with neurotransmitter vesicles that pass near or on the surface of effector cells (i.e. smooth muscle Membrane receptors scattered on the surfaces of effector cells respond to the neurotransmitter, causing cellular action

Different neurotransmitters are released at axon terminals, binding to different types of receptors, facilitating specific actions on target cells and tissues (on or off) Their duration of action is variable and is dependent on their reabsorption by varicosities or inactivation by enzymes (monoamine oxidase or catechol-o-methyltrasnferase) In general, systemically released agents remain active for a longer period of time due to poor reuptake or degradation in the systemic fluid (i.e. epinephrine from the adrenal medulla into blood)

Sympathetic Stimulation and the Release of Norepinephrine (NE) and Epinephrine (Epi)
Adrenergic Alpha-1 (a1) receptors are more common and better agonized by NE Stimulation causes a release of intracellular calcium ions from reserves in the endoplasmic reticulum It has an excitatory effect on the target cell Adrenergic Alpha-1 (a2) receptors are less common Stimulation causes a reduction in cAMP levels in the cytoplasm, producing an inhibitory effect The presence of a2 receptors in the parasympathetic division helps coordinate sympathetic responses (the same agonist turns on/off tissue due to receptor)

Sympathetic Stimulation and the Release of Norepinephrine (NE) and Epinephrine (Epi)
Adrenergic Beta () receptors Affect membranes in many organs (skeletal muscles, lungs, heart, and liver) Trigger metabolic changes in target cell Stimulation increases intracellular cAMP levels There are three types of Beta receptors Beta-1 (1) increases metabolic activity Beta-2 (2) triggers relaxation of smooth muscles along the respiratory tract Beta-3 (3) leads to lipolysis, the breakdown of triglycerides in adipocytes

Sympathetic Stimulation and the Release of Acetylcholine (Ach) and Nitric Oxide (NO)
Cholinergic (ACh) sympathetic terminals Innervate sweat glands of the skin and blood vessels of the skeletal muscles and brain They stimulate sweat gland secretion and dilate blood vessels Nitroxidergic synapses Release nitric oxide (NO) as neurotransmitter These neurons innervate smooth muscles in walls of blood vessels in skeletal muscles and the brain They produce vasodilation and increase blood flow

16-4 The Parasympathetic Division
Preganglionic neurons originate in the brain stem and sacral segments of the spinal cord. That is why the Parasympathetic Division is referred to as “craniosacral” These long preganglionic fibers ventrally exit and synapse in ganglia close to or near the target organ; Acetylcholine is the neurotransmitter Next, short postganglionic neurons originate in ganglia and terminate near (terminal ganglion) or on (intramural ganglion) target organs; Acetylcholine is the neurotransmitter This division prepares the body for relaxation, producing a “rest or digest” response

Parasympathetic Responses
There are five responses to increased Parasympathetic activity (“rest or digest”) Decreased metabolic rate Decreased heart rate and blood pressure Increased secretion by salivary and digestive glands Increased motility and blood flow in digestive tract Urination and defecation stimulation

Organization and Anatomy of Parasympathetic Division
Parasympathetic preganglionic fibers leave the brain as components of cranial nerves CN III (oculomotor), CN VII (facial), CN IX (glossopharyngeal) and CN X (vagus) The Oculomotor, Facial and Glossopharyngeal nerves control visceral structures in the head. They synapse in ciliary, pterygopalatine, submandibular, and otic ganglia whose short postganglionic fibers continue to their peripheral targets The Vagus nerve provides preganglionic parasympathetic innervation to structures in the neck, thoracic and abdominopelvic cavities (as distant as a distal portion of large intestine). Branches intermingle with fibers of the sympathetic division [the vagus nerve provides 75 percent of all parasympathetic outflow!] Parasympathetic preganglionic fibers leave the spinal cord at the sacral level and do not join ventral roots of spinal nerves. Instead, they form pelvic nerves that innervate the intramural ganglia in the walls of the kidneys, urinary bladder, portions of the large intestine and the sex organs

Pterygopalatine ganglion
The innervation of the parasympathetic division on one side of the body; the innervation on the opposite side (not shown) follows the same pattern KEY Preganglionic neurons Ganglionic neurons Pterygopalatine ganglion CN III Lacrimal gland Eye Ciliary ganglion PONS CN VII Submandibular ganglion Salivary glands CN IX Otic ganglion Vagus nerve (CN X) which provides about 75 percent of all parasympathetic outflow Heart Cardiac and Pulmonary plexus Lungs Celiac plexus Spinal cord Liver and gallbladder Stomach Inferior mesenteric plexus Spleen Pancreas Hypogastric plexus Large intestine Preganglionic fibers in the sacral segments of the spinal cord, which carry sacral parasympathetic output Small intestine Rectum S2 Kidney S3 S4 Penis Uterus Ovary Scrotum Urinary bladder 29

Paraympathetic Summary
Parasympathetic (Craniosacral) Division of ANS Preganglionic Neurons Ganglionic Neurons Target Organs N III Nuclei in brain stem Ciliary ganglion Intrinsic eye muscles (pupil and lens shape) N VII Pterygopalatine and submandibular ganglia Nasal glands, tear glands, and salivary glands N IX Otic ganglion Parotid salivary gland N X Intramural ganglia Visceral organs of neck, thoracic cavity, and most of abdominal cavity Nuclei in spinal cord segments S2–S4 Pelvic nerves Visceral organs in inferior portion of abdominopelvic cavity KEY Intramural ganglia Preganglionic fibers Postganglionic fibers 30

Major Effects of the Parasympathetic Division
Constriction of the pupils restricts the amount of light that enters the eyes Lens adjustment facilitates focusing of the eyes on nearby objects Secretion by digestive glands (including salivary glands, gastric glands, duodenal glands, intestinal glands, the pancreas (exocrine and endocrine), and the liver) Secretion of hormones that promote the absorption and utilization of nutrients by peripheral cells Changes in blood flow and glandular activity associated with sexual arousal Increase in smooth muscle activity along the digestive tract Stimulation and coordination of defecation Contraction of the urinary bladder during urination Constriction of the respiratory passageways Reduction in heart rate and in the force of contraction

16-5 Parasympathetic Neurons Release ACh
All neuromuscular and neuroglandular junctions employ acetylcholine as a neurotransmitter The space within the junction is small and confined, and filled with degrading enzymes (acetylcholinesterase) Thus, the effects of stimulation are short lived (as compared to the effects of systemic stimulation by the neurotransmitter epinephrine)

Parasympathetic Stimulation and the Release of Acetylcholine (Ach)
Nicotinic receptors are on the surfaces of sympathetic and parasympathetic ganglion cells Exposure to ACh causes excitation of ganglionic neurons or muscle fibers Muscarinic receptors are on all parasympathetic neuromuscular or neuroglandular junctions and at a few sympathetic cholinergic junctions Effects last longer than nicotinic receptors (G protein driven signal transduction cascade) They can be excitatory or inhibitory, depending on the intracellular enzymes activated when the ligand binds the receptor

Dangerous Environmental Toxins
Toxins produce exaggerated and uncontrolled responses Nicotine binds to nicotinic receptors (i.e. tobacco) It targets autonomic ganglia and skeletal neuromuscular junctions Death may result from an injestion of 50 mg Signs and symptoms include vomiting, diarrhea, high blood pressure, rapid heart rate, sweating, profuse salivation, convulsions Muscarine binds to muscarinic receptors (i.e. mushrooms) It gargets parasympathetic neuromuscular or neuroglandular junctions Signs and symptoms include salivation, nausea, vomiting, diarrhea, constriction of respiratory passages, low blood pressure, slow heart rate (bradycardia)

Summary: Adrenergic and Cholinergic Receptors of the ANS

16-6 Dual Innervation by both Divisions
The sympathetic division shows extensive divergence. A single preganglionic fiber can innervate many post-ganglionic fibers, resulting in a long lasting and broad array of control in organs and tissues throughout In contrast, the parasympathetic division is restricted. Preganglionic fibers of the parasympathetic division do not diverge as extensively and as a result, their effect is brief and more specific (certain visceral structures) Certain vital organs (thoracic and abdominopelvic) receive opposing instructions from both divisions; this is important as the two divisions commonly have opposing effects, functionally bringing us to the concept of autonomic tone. But first comes the anatomy…

Anatomy of Dual Innervation
After reaching their respective ganglion, parasympathetic and sympathetic postganglionic fibers travel via cranial nerves to peripheral destinations in the thoracic and abdominopelvic cavities (heart, lungs, gut, bladder and reproductive organs Due to the anatomic differences in fiber length between the sympathetic and parasympathetic divisions, the sympathetic postganglionic fibers mingle with the parasympathetic preganglionic fibers, forming a series of nerve networks collectively called autonomic plexuses (cardiac, pulmonary, esophageal, celiac, inferior mesenteric and hypogastric plexuses) I can see you’re confused; let’s backtrack for a moment

Two important anatomical points:
Summary: A Structural Comparison of the Sympathetic and Parasympathetic Divisions of the ANS Two important anatomical points: Length of pre- and postganglionic fibers Neurotransmitters used at junctions Sympathetic Parasympathetic Preganglionic fibers Postganglionic fibers

Important Anatomical Point
Summary: The Anatomical Differences between the Sympathetic and Parasympathetic Divisions. Important Anatomical Point Since sympathetic preganglionic fibers are short* and parasympathetic preganglionic fibers are long*, there is an overlapping area between the sympathetic postganglionic fiber and the parasympathetic preganglionic fiber These fibers “mingle”, forming a series of nerve networks collectively referred to as autonomic plexuses (next slide) Nerves leaving these networks travel with the blood and lymphatic vessels that supply the viscera * * overlap area

HEART LUNG ESOPHAGUS VISCERA DIGEST URINARY REPRODUCTIVE Trachea
Left vagus nerve HEART Thoracic spinal nerves LUNG Esophagus ESOPHAGUS Splanchnic nerves VISCERA Diaphragm Superior mesenteric artery Inferior mesenteric artery DIGEST URINARY REPRODUCTIVE

Autonomic Tone and Dual Innervation
Autonomic tone is an important aspect of the autonomic nervous system If a nerve is inactive under normal conditions, it can only increase activity But if a nerve maintains a background level of activity, it can increase or decrease activity Thus, autonomic motor neurons maintain a resting level of spontaneous activity (where the background level of activation determines autonomic tone)

…Example of Tone and Dual Innervation
The heart receives dual innervation; the two divisions have opposing effects on the heart The parasympathetic division slows the heart rate. The sympathetic division accelerates the heart rate This reflects a balance between the two divisions. Autonomic tone allows for a range in activity Under relaxed conditions, parasympathetic innervation dominates. When stressed, the sympathetic system is engaged and the parasympathetic system is relieved.

Summary: A Functional Comparison of the Sympathetic and Parasympathetic Divisions of the ANS
Sympathetic effects!

Sympathetic effects!

16-7 Visceral Reflexes Regulate the ANS
Like somatic reflexes, visceral reflexes provide automatic motor responses They can be modified, facilitated, or inhibited by higher centers, especially the hypothalamus There are two types of visceral reflex arcs, each containing a receptor, sensory neuron, polysynaptic processing centers (one or more interneurons) and two visceral motor neurons Long reflexes Short reflexes

Long reflexes Long reflexes are autonomic equivalents of polysynaptic reflexes Visceral sensory neurons deliver information to the CNS along the dorsal roots of spinal nerves (The visceral sensory nerurons are within sensory branches of cranial nerves or within autonomic nerves that innervate visceral effectors) The ANS carries motor commands to visceral effectors to coordinate the activities of the entire organ

Short reflexes Short reflexes bypass the CNS, involving sensory neurons and interneurons located within the autonomic ganglia Ganglionic interneurons synapse on ganglionic neurons, where the motor commands are distributed by postganglionic fibers This controls simple motor responses with localized effects, affecting one small part of a target organ

…Example of short reflexes (digestive tract)
In most organs, long reflexes are the most important In the digestive tract, short reflexes provide the most control and coordination of peristalisis (as we will soon discuss, the CNS still has some control over digestion) Ganglia in the walls of the digestive tract contain cell bodies of visceral sensory neurons (visceral plexes), interneurons and motor neurons. The axons form extensive nerve nets that control digestive functions independent of the central nervous system

Summary: Representative Visceral Reflexes

Higher Levels of Autonomic Control
Like the somatic system, simple reflexes from the spinal cord provide rapid and automatic responses to stimuli Processing centers in the medulla oblongata coordinate more complex sympathetic and parasympathetic reflexes In addition to the cardiovascular and respiratory centers, it contains centers and nuclei involved in many other autonomic functions (salivation, swallowing, digestive secretions, peristalisis, urination). These centers are in turn subject to regulation by the hypothalamus. Since the hypothalamus interacts with the limbic system, emotions can have a dramatic effect on autonomic function (i.e. angry?  upset stomach)

The Integration of SNS and ANS Activities
There are many parallels in the organization and function of nervous system activities That is because they are integrated in the brain stem Thus, both systems under control of higher centers

Summary: A Comparison of Somatic and Autonomic Function

Summary: A Comparison of the Autonomic and Somatic Nervous System

Summary: Efferent Divisions of the Nervous System
Somatic Autonomic Effectors – Skeletal muscles Effectors – Smooth, Cardiac muscles and glands Conscious (voluntary) and Unconscious regulation Unconscious (Involuntary) regulation Excitatory action – skeletal muscle contracts Excitatory and Inhibitory action of target tissues Single synapse Two synapses – preganglionic and ganglionic neurons Neurotransmitter- Acetylcholine Neurotransmitter - Acetycholine by preganglionic neurons and ACh or norepinephrine/epinephrine by postganglionic neurons Seldom effects long term survival Critical for homeostasis and survival

Summary: Differences Between Somatic and Autonomic Nervous Systems
Central nervous system Peripheral nervous system Effector organs Acetylcholine Somatic nervous system Skeletal muscle Acetylcholine Norepinephrine Smooth muscle (e.g., in stomach) Sympathetic division Ganglion Acetylcholine Epinephrine and norepinephrine Autonomic nervous system Blood vessel Glands Adrenal medulla Acetylcholine Cardiac muscle Parasympathetic division Ganglion KEY: Preganglionic axons (sympathetic) Postganglionic axons (sympathetic) Myelination Preganglionic axons (parasympathetic) Postganglionic axons (parasympathetic)

16-8 Higher-Order Functions
Higher-order functions share three characteristics They require the cerebral cortex Involve the conscious and unconscious processing of information by the Central Nervous System Are not part of the programmed “wiring” of the brain; in other words, they can adjust over time (plasticity)

Memory (and Learning) Memory is the process of encoding, storing and retrieving a sensory or motor experience, or thought Learning is the process by which we acquire information or skills as a result of instruction or experience. For learning to occur, we need to remember what we have experienced Thus, plasticity describes the ability of the nervous system to be modified after birth. At the cellular level, synaptic plasticity is the ability of a synaptic connection to change in response to an experience [where correlation is directly related to reinforcement]

There are two classes of memories:
Factual memories are specific bits of information (i.e. what is the color of a stop sign?) Skill memories are learned motor behaviors that, with repetition, are incorporated at an unconscious level Simple skill memories are stored in the brain stem (i.e. eating) Complex skill memories require integration of motor patterns in the basal nuclei, cerebral cortex and cerebellum (i.e. skiing) There are two classes of memories: Short-term memories do not last long, but while they persist, can be recalled, immediately (i.e. a person’s name) Long-term memories last much longer (some for a lifetime) and are created from short-term memories (memory consolidation) There are two types of long-term memory: Secondary memories fade and require effort to recall Tertiary memories remain with you for life

Figure 16-13 Memory Storage
Repetition promotes retention Long-term Memory Short-term Memory Sensory input Secondary Memory Tertiary Memory Consolidation • Cerebral cortex (fact memory) • Cerebral cortex and cerebellar cortex (skill memory) Temporary loss Permanent loss due to neural fatigue, shock, interference by other stimuli Permanent loss 59

Brain Regions Involved in Memory Consolidation & Access
There are two principal brain regions involved in memory consolidation and access: In the Limbic System… The amygdala is linked with emotion-bound memories The hippocampus is linked with short-term to long-term conversion of memories (then stored in the cerebrum) In the Cerebrum… Association areas store conscious motor and sensory memories (i.e. occipital and temporal areas associate with facial, voice and word recognition) The nucleus basalis bears an uncertain role (but it is interconnected with the other players in memory)

Cellular Mechanisms of Memory Formation and Storage
Memory consolidation involves anatomic and physiologic changes in neurons and synapses, thereby facilitating communication along a specific neural circuit (engram) Three cellular mechanisms are implicated: Frequently active pre-synaptic neurons increase neurotransmitter storage and release when stimulated This increased synaptic activity causes the depolarization of the post-synaptic neuron, resulting in synaptic facilitation, affecting all the neurons in the circuit Increased synaptic activity also facilitates the formation of additional synaptic connections (more receptors), enhancing neuronal networking (synaptic plasticity), resulting in long term potentiation (LTP) of the memory engram [hippocampus; glutamate neurotransmitter binds NMDA receptors, increasing neuron calcium intake, triggering second messenger cascades]

A Schematic Representation of Plasticity and LTP
A synapse is repeatedly stimulated with neurotransmitter from a pre-synaptic neuron (in this case, glutamate)

In response, more dendritic receptors (NMDA) are produced on the post-synaptic neuron of the synapse

Due to persistent stimulation, the pre-synaptic neuron releases an increasing amount of neurotransmitter

A stronger link is formed between neurons (synaptic plasticity), resulting in Long Term Potentiation (increased second messenger cascade via Ca+2)

Some Tips on Memory Enhancement
Memories form as a result of experience and repetition. This depends on the nature, intensity and frequency of the original stimulus: strong, repeated and exceedingly pleasant or unpleasant events will likely be converted to long-term memories Some consolidation of memory is thought to occur during sleep. Thus, you should rest after studying for an exam Drugs such as caffeine and nicotine enhance memory consolidation through facilitation (the jury is still out on heavier stuff, like adderallTM or other amphetamines)

Amnesia Amnesia is the loss of memory due to trauma or disease in the learning circuit Anterograde amnesia is a loss of memory for events that occur after a trauma (the inability to form new memories) Retrograde amnesia is a loss of memory for events that occur before a trauma (an inability to recall past events)

States of Consciousness
There are many gradations of states of consciousness and unconsciousness A conscious individual can be nearly asleep, wide awake or anxious An unconscious individual can be unresponsive, deep or lightly asleep The degree of wakefulness indicates the level of ongoing Central Nervous System activity Under normal conditions, an unconscious individual can be awakened by normal stimuli (i.e. an alarm clock) When CNS function becomes abnormal or depressed, state of wakefulness can be affected (i.e. in a coma or under anesthetic)

Sleep Sleep has an important impact on the Central Nervous System; extended periods without sleep lead to disturbances in mental function There are two general levels of sleep, each with a characteristic pattern of brain wave activity Deep sleep is also called slow-wave or Non-REM (NREM) sleep. During deep sleep, the entire body relaxes and cerebral cortex activity is minimized Rapid eye movement (REM) sleep is when active dreaming occurs. Hallmarks of REM include decreased muscle tone, irregularities in blood pressure, respiration and eye movements, and reduced reception to outside stimuli

Sleep – some points… The REM state EEG pattern resembles the alpha wave pattern that is typical of normal, awake adults Periods of REM and deep sleep alternate throughout the night, with a transitional period between them and the REM state increasing in duration A normal adult will dream for roughly one quarter of their sleep cycle

Arousal and the Reticular Activating System
The reticular formation plays a significant role as the “watchdog” during arousal (the awakening from sleep) Due to its anatomic location, it receives sensory, motor and integrative information That information is fed through the reticular activating system to the thalamus, and then radiated to areas of the cerebral cortex (activation therein) The RF extends from the medulla oblongata to the midbrain

Regulation of sleep – awake cycles
After many hours, the reticular formation becomes less responsive to stimulation, and the individual becomes less alert and more lethargic (neural fatigue reduces RAS activity) This involves an interplay between specific brain stem nuclei that use different neurotransmitters (“dueling” between nuclei) One group of nuclei stimulates the RAS with NE and maintains the awake, alert state Another group of nuclei depresses RAS activity with serotonin, promoting deep sleep

16-9 Brain Chemistry Changes in the normal balance between two or more neurotransmitters can profoundly affect brain function This pathology can be explained, etiologically, from genetic and environmental factors Disorders of the nervous system include Huntington’s disease, schizophrenia, depression, drug addiction, Alzheimer’s and Parkinson’s diseases

Huntington’s Disease Huntington’s Disease is a late onset, progressive, lethal genetic disease It is characterized by the destruction of ACh-secreting and GABA-secreting neurons in the basal nuclei Symptoms appear as the basal nuclei and frontal lobes slowly degenerate (and disappear) Patients have difficulty controlling movements and experience a gradual decline in intellect

Euphoria Variations in brain serotonin levels affect sensory interpretation and emotional states Compounds that enhance the effects of serotonin produce happiness (and hallucination) Lysergic acid diethylamide (LSD) is a powerful hallucinogen that activates serotonin receptors in the brain stem, hypothalamus and limbic system Serotonin reuptake inhibitors (SSRI’s) like fluoxetine (Prozac), Celexa, Luvox, Paxil and Zoloft, slow the removal of serotonin at synapses

Depression Depression is a common disorder associated with feelings of sadness and pain that interferes with everyday life Two broad forms of depressive illness are known: Patients with major depressive disorder have a persistent lack of interest or pleasure in most activities Bipolarity is characterized by mania (high-mood) and depressive (low-mood) phases Since depression is associated with inbalances of serotonin or norepinephrine, SSRI’s are employed

Schizophrenia Schizophrenia, a common disorder affecting roughly one percent of the world’s population, is associated with excessive dopamine production It is characterized by abnormal social behavior and a failure to understand reality Common symptoms include false beliefs, unclear or confused thinking, hearing voices, reduced social engagement and emotional expression, and a lack of motivation People often have additional mental health problems such as anxiety disorders, major depressive illness or substance abuse Symptoms typically come on gradually, begin in young adulthood, and last a long time. Available treatments focus on brain pathways that use dopamine as a neurotransmitter

Of note: Amphetamines produce schizophrenic symptoms

Drug Use, Addiction and Reward
Many abused drugs alter your mood by changing the concentrations of specific neurotransmitters in the brain (serotonin, dopamine, norepinephrine) This results in an increased activity of the brain’s reward system (limbic system) and is the basis of psychological addiction

Supplemental: The Limbic System
Functions of the Limbic system include… Memory consolidation, access and learning: (amygdala and hippocampus) Creation of emotions: (rage, fear, pain, sexual arousal, pleasure) It receives processed information from the general and special senses and generates an emotional response Amygdala: several emotional responses, especially fear Nucleus accumbens: gratification centers sends output to the hypothalamus, lower brainstem and prefrontal cortex Motivation and Drives: reward centers give us pleasure when carrying out vital tasks such as eating, drinking, sexual activity. Input is from dopaminergic neurons in the midbrain (ventral tegmented area)

16-10 Aging Specific anatomical and physiological changes begin after maturity (age 30) and progress with age These include: A reduction in brain size and weight A reduction in the number of neurons A decrease in blood flow to the brain (CVA; stroke) Changes in synaptic organization of the brain Intracellular and extracellular changes in CNS neurons (markedly observed Alzheimer’s disease)

Eighty-five percent of people over age 65 have changes in mental performance and Central Nervous System function Anatomical changes are correlated with deficits in neural processing, memory consolidation and access Sensory systems become less acute, reaction times slow and reflexes weaken Motor control diminishes, effecting precision and task/time management Eventually, incapacitation will ensue, but 85% of the elderly population develops changes that do not interfere with normal daily life!

Senility Senility is also referred to as senile dementia
It is correlated with particular degenerative changes: Memory loss Anterograde amnesia (can’t store new memories) Emotional disturbances Alzheimer’s disease

Alzheimer’s Disease Alzheimer’s is a progressive disorder characterized by the loss of higher-order cerebral functions, confusion, memory loss, and changes in mood and behavior Generally, symptoms appear in the 50’s; an estimated 2 million people are affected in the United States Pathologically, Alzheimer’s is associated with: A loss of acetylcholine producing neurons in the hippocampus and cerebral cortex (brain shrinkage) The accumulation of abnormal intracellular deposits in neurons Lipofuscin (granular pigment – function unknown) Neurofibrillary tangles and filaments inside the neuron cell body (associate with Tau protein) Amyloid plaques between neurons in the brain (associated with Beta-amyloid protein)

Amyloid plaque Neurofibrillary tangle 20 m

Postganglionic neuron
Upper motor neurons in primary motor cortex Visceral motor nuclei in hypothalamus Brain Brain Somatic motor nuclei of brain stem Preganglionic neuron Visceral Effectors Smooth muscle Autonomic nuclei in brain stem Glands Autonomic ganglia Skeletal Muscle Spinal cord Lower motor neurons Cardiac muscle Nuclei in ganglia Spinal cord Somatic motor nuclei of spinal cord Adipocytes Autonomic nuclei in spinal cord Postganglionic neuron Preganglionic neuron 1o Origin is for Central Control: Motor Cortex or Hypothalamus 2o Origin is for Reflexive Control: Stem or Spinal Cord Effectors Responding: Skeletal Muscle or Visceral Effectors Innervation: Direct or Indirect with Ganglion (pre/post gang n.) a Somatic nervous system b Autonomic nervous system

Thoracic organs Visceral and Exterior effectors Abdominopelvic organs
sympathetic chain ganglia collateral ganglion adrenal medullae Eye PONS Salivary glands Sympathetic nerves (CN 3, 7, 9, 10) Cervical sympathetic ganglia Superior Middle Thoracic organs 3C Heart Inferior T1 Cardiac and pulmonary plexuses Splanchnic nerves Celiac ganglion Lung Superior mesenteric ganglion Visceral and Exterior effectors Liver and gallbladder 12T Spinal cord Stomach Spleen Pancreas Abdominopelvic organs Large intestine Postganglionic fibers to spinal nerves (innervating skin, blood vessels, sweat glands, arrector pili muscles, adipose tissue) Inferior mesenteric ganglion Small intestine 5L L2 Adrenal medulla Adrenal medulla 5S Sympathetic chain ganglia Kidney 1C Ovary Coccygeal ganglia (Co1) fused together Penis Uterus Urinary bladder Scrotum Apporoximately 26 total ganglion Paired “chain” ganglia Single “collateral” ganglion KEY Preganglionic neurons Ganglionic neurons 89

Figure 16-3 The Organization of the Sympathetic Division of the ANS
Sympathetic Division of ANS Ganglionic Neurons Target Organs Preganglionic Neurons Visceral effectors in thoracic cavity, head, body wall, and limbs Sympathetic chain ganglia (paired) Lateral gray horns of spinal segments T1–L2 Collateral ganglia (unpaired) Visceral effectors in abdominopelvic cavity Adrenal medullae (paired) Organs and systems throughout body KEY Preganglionic fibers Postganglionic fibers Hormones released into circulation 90

Figure 16-5 Sympathetic Varicosities.
Preganglionic fiber (myelinated) Ganglionic neuron Postganglionic fiber (unmyelinated) Ganglion Varicosities Vesicles containing norepinephrine (NE) Mitochondrion Schwann cell cytoplasm 5 μm Smooth muscle cells Varicosities

Parasympathetic Division
Figure 16-2 Overview of the Autonomic Nervous System (Part 2 of 2). Parasympathetic Division (Craniosacral) Preganglionic Neurons Preganglionic neurons in brain stem and in lateral portion of anterior gray horns of S2–S4. Ganglia Ganglia are in or near the target organ. Preganglionic fibers release acetylcholine (Ach), stimulating ganglionic neurons. Target Organs All postganglionic fibers release Acetylcholine at neuroeffector junctions. Parasympathetic stimulation “Rest and digest” response KEY Preganglionic fibers Postganglionic fibers

Figure 16-8 The Autonomic Plexuses and Ganglia (Part 1 of 2).
Aortic arch Right vagus nerve Trachea Autonomic Plexuses and Ganglia Left vagus nerve Cardiac plexus Thoracic spinal nerves Pulmonary plexus Esophagus Thoracic sympathetic chain ganglia Esophageal plexus Splanchnic nerves Celiac (solar) plexus and ganglion Superior mesenteric ganglion Diaphragm Superior mesenteric artery Inferior mesenteric plexus and ganglia Inferior mesenteric artery Hypogastric plexus Pelvic sympathetic chain

Sympathetic Parasympathetic CNS Preganglionic neuron PNS
Summary: The Anatomical Differences between the Sympathetic and Parasympathetic Divisions. Sympathetic Parasympathetic CNS Preganglionic neuron PNS Preganglionic fiber KEY Sympathetic ganglion Neurotransmitters Acetylcholine Norepinephrine or Epinephrine Ganglionic neurons Bloodstream Postganglionic fiber Parasympathetic ganglion TARGET

Long reflex Receptors in peripheral tissue Afferent (sensory) fiber
CENTRAL NERVOUS SYSTEM Stimulus Long reflex Short reflex Processing center in spinal cord Peripheral effector Response Autonomic ganglion (sympathetic or parasympathetic) Postganglionic neuron Preganglionic neuron

Short reflex Receptors in peripheral tissue Afferent (sensory) fiber
CENTRAL NERVOUS SYSTEM Stimulus Long reflex Short reflex Processing center in spinal cord Peripheral effector Response Autonomic ganglion (sympathetic or parasympathetic) Postganglionic neuron Preganglionic neuron

Summary: A Comparison of Somatic and Autonomic Function
Central Nervous System Cerebral cortex Limbic system Thalamus Hypothalamus Somatic sensory Visceral sensory Relay and processing centers in brain stem Somatic reflexes Long reflexes Lower motor neuron Preganglionic neuron Peripheral Nervous System Sensory pathways SNS ANS Short reflexes Ganglionic neuron Skeletal muscles Sensory receptors Visceral effectors 97

Lecture Presentation by LeeAnn Frederick

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Lecture Presentation by LeeAnn Frederick

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