Physiology of excitable tissues (Introduction, Muscles, Nerves, CNS) copy.pdf

Distribution of GABA receptors Subtype of Location Function GABA receptor GABAA (ligand...

Distribution of GABA receptors Subtype of Location Function GABA receptor GABAA (ligand Binding opens Cl- channels CNS, placenta, immune cells, liver, bone gated ion site of action of sedative-hypnotics, alcohol, general growth plates channel) anesthetics GABAB (G Largely inhibitory by opening K+ channels or Widely distributed throughout the brain and protein-coupled closing Ca2+ channels autonomic NS receptor) modulates motor neuron excitability GABAC (ligand In many parts of the brain including the gated ion superior colliculus, cerebellum, hippocampus, Neuronal inhibition channel) and, most prominently, the retina GABA, which is synthesized from glutamic acid, is the chief inhibitory neurotransmitter in the brain and spinal cord. The functions of GABA include regulation of neuronal excitability throughout the CNS and motor coordination. 2. G-protein linked receptors (metabotropic) G-protein-coupled receptors are the largest class of receptors. G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane. Heterotrimeric G proteins have three subunits: α, β, and γ. When a signaling molecule binds to a G-protein- coupled receptor in the plasma membrane, a GDP22 molecule associated with the α subunit is exchanged for GTP23. The β and γ subunits dissociate from the α subunit, and a cellular response is triggered either by the α subunit or the dissociated β pair. https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biolo Hydrolysis of GTP to GDP terminates the signal. gy/Map%3A_Raven_Biology_12th_Edition/09%3A_Cell_Communicati on/9.02%3A_Receptor_Types/9.2C%3A_Types_of_Receptors Neurotransmitters, biogenic amines, lipids, proteins, amino acids, hormones, nucleotides etc. Histamine (H) receptors Histamine receptors ar one type of G-protein linked receptors. Histamine is formed in various cell types and is involved in numerous actions via binding to four receptor types, designated as H1–H4. https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.14524 22 GDP is the product of GTP and is involved in signal transduction. 23 GTP is essential to signal transduction, in particular with G-proteins, in second-messenger mechanisms where it is converted to guanosine diphosphate (GDP) through the action of GTPases. 31  Distribution of histamine receptors Subtype of histamine Location Function receptor Smooth muscle (intestine, contraction airway, uterus) blood vessels (endothelium release of NO and PGI2 – vasodilatation Blood vessels (widening of increased capillary permeability. gap junctions) H1 (G protein-coupled Blood vessels (smooth receptor) vasoconstriction muscle) afferent nerve endings stimulation ganglionic cell stimulation adrenal medulla release of CAs Brain transmitter gastric glands acid secretion blood vessels (smooth dilatation muscle) H2 (G protein-coupled heart – atria +ive chronotropy receptor) ventricles +ive inotropy uterus relaxation Brain transmitter Brain (presynaptically) inhibition of histamine release – sedation lung, spleen, skin, gastric decrease histamine release H3 (G protein-coupled mucosa receptor) inhibition of ACh release from myenteric ileum plexus neurones certain blood vessels inhibit NA release – vasodilatation regulates neutrophil release from bone H4 (G protein-coupled highly expressed in bone marrow, mediate eosinophil shape change and mast receptor) marrow and white blood cells cell chemotaxis Distribution of opioid receptors Opioid receptors are a group of inhibitory G protein-coupled receptors with opioids as ligands. Opioid peptides are peptides that bind to opioid receptors in the brain; opiates and opioids mimic the effect of these peptides. Such peptides may be produced by the body itself, for example endorphins. Opioid receptors are distributed widely in the brain, in the spinal cord, on peripheral neurons, and digestive tract. Opioid receptor Location Function Widely distributed in the brain. The highest levels are in the thalamus and in the Analgesia (supraspinal mu1 + spinal mu2); limbic system and basal ganglia, including respiratory depression (mu2); sedation; euphoria; Mu (G protein-coupled the amygdala, nucleus accumbens, anterior miosis; reduced GI motility (mu2), changes smooth receptor) cingulate cortex, and substantia gelatinosa muscle tone; physical dependence (morphine type), in the dorsal horn of the spinal cord, nausea, vomiting mesenterix plexus, sub-mucosal plexus, intestinal tract Analgesia (spinal kappa1) (supraspinal – CNS: striatum, thalamus, kappa3); respiratory depression (lower ceiling); Kappa (G protein-coupled hypothalamus, cerebral cortex, cerebellum dysphoria, psychotomimetic; miosis (lower receptor) and brainstem areas, spinal cord, mesenteric ceiling); sedation; physical dependence (nalorphine plexus type); reduced GI motility Analgesia (spinal + affective component of Delta (G protein-coupled CNS: cerebral cortex, spinal cord, supraspinal); respiratory depression; affective receptor) mesenteric plexus behavior; reinforcing action; reduced GI motility 32  3. Enzyme-linked (kinase-linked) receptors Enzyme-linked receptors are another kind of cell- surface receptor. They work with proteins, called enzymes, which play a major role in accelerating chemical reactions within cells. These reactions help cells assemble and dissemble material as well as grow and reproduce. Have an extracellular binding site for chemical signals. Enzyme-linked receptors have intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme or the enzyme-linked receptor has an intracellular https://www.ncbi.nlm.nih.gov/books/NBK10989/#:~:text domain that interacts directly with an enzyme. =Membrane%2Dimpermeant%20signaling%20molecul The enzyme-linked receptors normally have large es%20can,%2Dcoupled%20receptors%20(C). extracellular and intracellular domains. When a ligand binds to the extracellular domain, a signal is transferred through the membrane and activates the enzyme, which sets off a chain of events within the cell that eventually leads to a response. E.g., tyrosine kinase receptor, epidermal growth factor receptor. An example of this type of enzyme-linked receptor is the tyrosine kinase receptor. The tyrosine kinase receptor transfers phosphate groups to tyrosine molecules. Tyrosine kinase is an enzyme, which catalyzes phosphorylation from nucleoside triphosphate (ATP) to the amino acid tyrosine in proteins. Tyrosine is a nonessential amino acid the body makes from another amino acid called phenylalanine. It is an essential component for the production of several important brain chemicals called neurotransmitters, including epinephrine, norepinephrine, and dopamine. Nuclear (intracellular) receptors Nuclear receptors are receptors located inside the cell. These receptors are found either in the cytoplasm (Type I) or the nucleus (Type II) of a cell. Type I intracellular receptors are translocated to the nucleus after stimulation by an agonist. Examples: androgen, glucocorticoid, mineralocorticoid, and progesterone https://open.lib.umn.edu/pharmacology/chap receptors. ter/nuclear-receptors/ Type II intracellular receptors located in Intracellular Receptors: the nucleus of a cell, even in the absence of agonists. Hydrophobic signaling molecules typically diffuse across the plasma Examples: retinoic acid, thyroid receptors. membrane and interact with intracellular receptors in the cytoplasm https://slideplayer.com/slide/16897836/ 33  REPEAT! Peripheral nervous system (PNS) PNS – Efferent Division Communication link by which CNS controls activities of muscles and glands Two divisions of PNS Autonomic nervous system (ANS) Involuntary branch of PNS Innervates cardiac muscle, smooth muscle, most exocrine glands, some endocrine glands, and adipose tissue Somatic nervous system Subject to voluntary control Innervates skeletal muscle Sympathetic Nervous Parasympathetic Nervous System System Fibers originate in thoracic Fibers originate from cranial and lumbar regions of and sacral areas of CNS spinal cord Most preganglionic fibers Preganglionic fibers are longer are short Long postganglionic fibers Very short postganglionic fibers Preganglionic fibers Preganglionic fibers release release acetylcholine (Ach) acetylcholine (Ach) which which binds to N- binds to N-cholinoreceptors on cholinoreceptors on postganglionic nerve fiber postganglionic nerve fiber Most postganglionic fibers Postganglionic fibers release release norepinephrine acetylcholine which binds to which binds to α1, α2, M-cholinoreceptors (M1, M3, β1,β2 adrenoreceptors at M5 stimulate; M2, M4 inhibit) the site of effector at the site of effector https://slideplayer.com/slide/14581627/ Sympathetic preganglionic fibers tend to be shorter than parasympathetic preganglionic fibers because sympathetic ganglia are often closer to the spinal cord while parasympathetic preganglionic fibers tend to project to and synapse with the postganglionic fiber close to the target organ. Receptors in ANS Tissues innervated by autonomic nervous system have one or more of several different receptor types for postganglionic chemical messengers Acetylcholine receptors (also known as cholinergic receptors; cholinoreceptors) consist of two main types: muscarinic receptors and nicotinic receptors. Nicotinic receptors (bind nicotine) Found on postganglionic cell bodies of all autonomic ganglia Opens cation channels→ Na+ flow is higher→ AP https://www.quora.com/What-are-the-differences- between-muscarinic-and-nicotinic-receptors 34  Nicotinic receptors are ionotropic, meaning that when acetylcholine binds to it, ions flow through it. It acts as a channel for positively charged ions, mainly sodium. This depolarizes the cell. You can find nicotinic receptors at neuromuscular junctions. They play an integral part in allowing your muscles to move. These receptors are also found in the brain, plus in both the sympathetic and parasympathetic nervous systems on post-ganglionic neurons. Muscarinic receptors (bind mushroom poison) Found on effector cell membranes (e.g., smooth muscle, cardiac muscle, glands) Several (five) types Muscarinic receptors have a different mechanism of action. Instead of becoming an ion channel for sodium, they use a G-protein. When ACh binds to the receptor, this special protein changes shape, which then allows it to phosphorylate various second messengers. There are five different types of muscarinic receptors. M1, M3 & M5 https://www.quora.com/What-are-the- are excitatory receptors. The two others, M2 and M4, are inhibitory. differences-between-muscarinic-and-nicotinic- You can find muscarinic receptors in the brain, heart and smooth receptors muscle. Like nicotinic receptors, they are found in both the parasympathetic and sympathetic nervous systems. Distribution of cholinoreceptors (Nicotinic) Subtype of nicotinic Location Function receptor NM (Ion channel-linked Depolarization of muscle end plate – Neuromuscular junctions receptors) contraction of skeletal muscle Autonomic ganglia (sympathetic, Depolarization – postganglionic parasympathetic) impulse NN (Ion channel-linked receptors) Adrenal medulla Catecholamine release CNS Site specific excitation or inhibition Distribution of cholinoreceptors (Muscarinic) Subtype of muscarinic Location Function receptor Autonomic ganglia Depolarization (late EPSP) M1 (G protein-coupled Gastric glands Histamine release, acid secretion receptor) Esophagus relaxation of lower esophageal sphincter CNS Learning, memory, motor functions SA node Hyperpolarization, decreased rate of impulse generation AV node Decreased velocity of conduction Atrium Shortening of AP duration, decreased contractility M2 (G protein-coupled Ventricle Decreased contractility (slight) receptor) Cholinergic nerve endings Decrease ACh release CNS Tremor, analgesia Visceral smooth muscle Contraction Esophagus Contraction of lower esophageal sphincter Visceral smooth muscle Contraction Iris Constriction of pupil M3 (G protein-coupled Ciliary muscle Contraction receptor) Exocrine glands Secretion Vascular endothelium Vasodilatation Esophagus Contraction of lower esophageal sphincter M4 (G protein-coupled CNS Direct regulatory action on K and Ca ion channels receptor) M5 (G protein-coupled Substantia nigra (CNS) May regulate dopamine release at terminals within the stratium receptor) 35  Andrenergic receptors – bind to norepinephrine (20%) and epinephrine (80%) https://doctorlib.info/physiology/medical/77.html o Alpha (α) receptors (α1, α2) ▪ α1→ excitatory In most sympathetic target tissues E.g., Constriction of skin and GI arterioles, dilation of pupils, etc. ▪ α2→ inhibitory Decreased motility in digestive tract o Beta (β) receptors (β1, β2, β3) ▪ β1→ excitatory Primarily in the heart (increased heart rate and force of contraction) ▪ β2→ inhibitory Dilation of skeletal muscle arterioles and bronchioles ▪ β3→ in adipose tissue Lipolysis Distribution of adrenergic (adreno) receptors Receptor subtype Tissue Response Smooth muscle: vascular, uterus, trigone, pilomotor, ureter, sphincters (gastrointestinal and bladder), eye (iris), radial, vas Contraction deferens Smooth muscle (gastrointestinal) Relaxation Glycogenolysis, gluconeogenesis, Liver ureagenesis α1 (G protein-coupled Myocardium Increased force of contraction receptor) Increased locomotor activity, Central nervous system neurotransmission Salivary glands Secretion (K+, H2O) Kidney (proximal tubule) Gluconeogenesis Adipose tissue Glycogenolysis Sympathetic nerve terminal Inhibition of norepinephrine release Vascular smooth muscle Contraction Platelets Aggregation, granule release Sedation, inhibition of sympathetic Central nervous system outflow, neurotransmission Adipose tissue Inhibition of lipolysis α2 (G protein-coupled Eye Decreased intraocular pressure receptor) Endothelium Release of vasodilator substance Jejunum Inhibition of secretion Kidney Inhibition of renin release Pancreatic islet cells Inhibition of insulin release Cholinergic neurons and cell bodies of noradrenergic neurons Inhibition of firing Inhibition of MSH-induced granule Melanocytes dispersion 36  Distribution of adrenergic (adreno) receptors Receptor subtype Tissue Response β1 (G protein-coupled Myocardium receptor) SA node Increase in heart rate Atria Increase in contractility and conduction velocity His-Purkinje system Increase in automaticity and conduction velocity Ventricles Increase in contractility, conduction, velocity, automaticity, and rate of idioventricular pacemakers Kidney Renin secretion Adipose tissue Lipolysis Posterior pituitary Antidiuretic hormone secretion Sympathetic nerve terminal Increased neurotransmitter release Stomach Increase ghrelin secretion β2 (G protein-coupled Smooth muscle: vascular, Relaxation receptor) uterus, gastrointestinal (stomach, intestine gallbladder and bile ducts), bladder (detrusor), lung (tracheal and bronchial) Skeletal muscle Increased contractility, glycogenolysis, K+ uptake Liver Glycogenolysis and gluconeogenesis Pancreas Insulin secretion Splenic capsule Relaxation Salivary glands Amylase secretion Lung: bronchial glands Increased secretion β3 (G protein-coupled Ileum Relaxation receptor) Fat cells Lipolysis Parasympathetic system Sympathetic system dominates in dominates in quiet, relaxed emergency or stressful (“fight-or- (“rest-and-digest”) situations flight”) situations Promotes body- Promotes responses that maintenance prepare body for activities such as strenuous physical digestion activity https://quizlet.com/372354428/chapter-11-efferent-division-autonomic-and-somatic- motor-control-diagram/ 37  Ligands A molecule that binds to a receptor is called a ligand, and it can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter, hormone, pharmaceutical drug, toxin, or parts of the outside of a virus or microbe. Ligands are able to fit into specific receptor sites in the same way keys are able to fit into specific locks. For example, dopamine binds to dopamine receptors, https://en.m.wikipedia.org/wiki/File:Proten_ligand_binding.PNG and insulin binds to insulin receptors, but they cannot bind to each other’s receptors. By binding to the receptor site, ligands are able to transmit information from a cell’s external environment and to its interior. Whenever a ligand binds to a receptor site, it alters the shape of the receptor and launches a cascade of chemical reactions known as signaling. A message from the ligand makes its way into the cell, which can induce a variety of responses, including changes in gene expression. Not all ligands that bind to a receptor always activate it. Agonists and antagonists The following ligands are known: 1. (Full) agonists are able to activate the receptor and result in a strong biological response (100% efficacy) (Full opioid agonist – methadone) 2. Partial agonists do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared to those of full https://pharmaeducation.net/agonist-partial-agonist-antagonist-inverse-agonist/ agonists (efficacy between 0 and 100%) (Partial opioid agonist – buprenorphine) 3. Antagonists bind to receptor but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists (H2 receptor antagonist – ranitidine) 4. Inverse agonists reduce the activity of receptors by inhibiting their constitutive activity (negative efficacy). An inverse agonist binds to the same receptor as an agonist but brings about an opposite response to that of the agonist. (beta adrenoceptor inverse agonist – carazolol) Full agonists Bind to a receptor and activate it (trigger a physiological response) E.g. Methadone Mu opioid receptors Analgesic effect Fentanyl Mu opioid receptors Analgesic effect 38  Partial agonists Do not activate receptors with maximal efficacy, even with maximal binding, causing partial responses compared to those of full agonists E.g. Buprenorphine Activates mu opioid receptors Analgesic effect Salbutamol Activates β2 receptors Treatment of asthma (relieve bronchospasms) In the presence of a full agonist, a partial agonist can actually reduce the overall response because the partial agonist competes with the full agonist for receptor binding sites. A great example of this is buprenorphine, which is a partial agonist at the mu receptor (an opioid receptor): it produces less of a response than other opioids, like morphine. Antagonists Bind to receptor but do not activate them. This results in a receptor blockade, inhibiting the binding of agonists and inverse agonists. E.g. Atenolol Selective β1 blocker Blockage produces bradycardia and decrease in blood pressure Ranitidine Acts on H2 receptors Reduces the production and secretion of gastric acid Inverse agonists Reduce the activity of receptors by inhibiting their constitutive activity (negative efficacy). An inverse agonist is a drug that binds to the same receptor as an agonist but brings about an opposite response to that of the agonist. There should be a prerequisite for an inverse agonist action upon a particular receptor. In other words, the receptor must have a constitutive level of activity without any ligand. An agonist increases the activity of a particular receptor above its basal level. An inverse agonist decreases the activity of a receptor below the basal level. E.g. Carazolol Acts on β adrenoceptors Used to prevent stress 39  Physiology of the CNS Nerve center The functional unit of the CNS is the nerve center. The CNS includes the brain and spinal cord along with various centers that integrate all the sensory and motor information in the body. A nerve center is a group of neurons that participate in the formation of a certain reflex or in regulation of a certain function. These centers can be broadly subdivided into lower centers, including the spinal cord and brain stem, that carry out essential body and organ-control functions and higher centers within the brain that control more sophisticated information processing, including our thoughts and perceptions. Nerve center is a physiological rather than an anatomical concept. E.g., the center of respiratory regulation in the CNS is located in 4 parts. They have the principle of subordination. Transmission of excitation in the CNS is realized through synapses. Parts of the CNS: the brain and spinal cord 1. Surrounded by bones, meninges (dura mater, arachnoid mater, pia mater). 2. The gaps are filled with cerebrospinal fluid. Cerebrospinal fluid is a clear fluid that acts as a cushion for the brain and maintains overall central nervous system homeostasis. It contains proteins and glucose that provide energy for brain cell function as well as https://teachmeanatomy.info/neuroanatomy/str lymphocytes that guard against infection. Circulation of the fluid uctures/meninges/ is aided by pulsations of the cerebral arteries. 3. During the embryonic development is formed from the neural tube. The spinal cord The lower part of the CNS. Phylogenetically is the oldest. The spinal cord is the most important structure between the body and the brain. The spinal cord extends from the foramen magnum where it is continuous with the medulla to the level of the first or second lumbar vertebrae. It is a vital link between the brain and the body, and from the body to the brain. The Spinal Cord transmits signals to and from the brain and commands reflexes. Very important for maintaining homeostasis. E.g., all sensory nerve fibers (afferent) enter directly in the spinal cord through dorsal (posterior) roots. The gray matter of the brain is organized in the central part (centers), outside – the white matter formed by the neuron axons (conducting pathways) Gray matter, is a major component of the CNS and is home to neural cell bodies, axon terminals, and dendrites, as well as all nerve synapses. White matter is composed mainly of bundles of myelinated axons, with very few neuronal bodies. While grey matter is primarily associated with processing and cognition, white matter modulates https://quizlet.com/552925283/lect-10-nervous-system-study- setpractice-questions-flash-cards/ the distribution of action potentials, acting as a relay and coordinating communication between different brain regions. Using a computer 40  network as an analogy, the grey matter can be thought of as the actual computers themselves, whereas the white matter represents the network cables connecting the computers together. Damage to the white matter of brain or spinal cord can affect the ability to move, use sensory faculties, or react appropriately to external stimuli. Research of the spinal cord The spinal cord is studied with so called «spinal animal» - an animal, usually a frog, dog, or cat, whose spinal cord has been transected, interupting the anatomical integrity of the spinal cord at transition place to the brain and causing the so-called spinal shock. Spinal shock: Reflexes that are regulated in the brain, receiving information through the spinal cord, disappear. Atony (lack of muscle tone) occurs caudal to the damaged area Loss of sensation, because sensations from the body are conducted through the spinal cord. Spinal cord reflexes are lost at the site of the lesion The more highly developed the animal, the more devastating the spinal shock is. Functions of the spinal cord 1. Reflex function Associated with nerve centers localized in the gray matter of the spinal cord. Many reflexes are realized through it: Somatic reflexes – the most prominent: Tendon reflex – used by neurologists to test the integrity of the reflex arc Muscle tone reflex – skeletal muscles are always in a toned state, because of the gravity. This reflex is realized through the spinal cord. Autonomic reflexes – are realized through the spinal cord. The lower centers of the sympathetic nervous system are located in thoracic and lumbar segments. The lower centers of the parasympathetic nervous system are located in sacral segments. Regulate, for example, sweating, urine output, defecation, erection, ejaculation. 2. Conduction function Provides communication between different parts of the CNS The conduction pathways of excitation are localized in the white matter of the spinal cord: Ascending (transfer information to the brain) Descending (transfer information to the periphery) If the conduction of impulses is disturbed, paralysis occurs. 41  The brain The brain, in conjunction with the spinal cord, regulates both nonconscious processes and coordinates most voluntary movement. Every second, millions of chemical and electrical signals pass around the brain and the body’s intricate nerve network. Anatomical classification of brain parts Cerebrum Cerebral hemispheres (cortex, white matter, basal ganglia) Brain stem Midbrain Pons Medulla Diencephalon Thalamus Hypothalamus slideplayer.com/slide/7402473/ Epithalamus Cerebellum Cerebrum The cerebrum consists of two cerebral hemispheres, the right and the left. The largest part of the brain containing the cerebral cortex, as well as several subcortical structures, including the hippocampus and basal ganglia. Functions: controls emotions, hearing, vision, all precision of voluntary actions with the assistance of the cerebellum, the https://neurological.org.nz/conditions/glossary/ cerebrum/ cerebrum controls all voluntary actions in the body. The cerebral cortex, the outer layer of grey matter of the cerebrum, is found only in mammals. Cerebral hemispheres Anatomists conventionally divide each hemisphere into four lobes: 1. the frontal (control of specialized motor control, learning, planning, and speech), 2. parietal (control of somatic sensory functions), 3. occipital (control of vision), 4. temporal lobes (control of hearing and some speech). The cerebrum is contralaterally organized, i.e., the right https://qbi.uq.edu.au/brain/brain-anatomy/lobes-brain hemisphere controls and processes signals from the left side of the body, while the left hemisphere controls and processes signals from the right side of the body. 42  Cerebral cortex A thin layer of gray matter covering the surface of the cerebral hemispheres. It is the highest part of the CNS, the most complex in structure (6 layers) and functions. Phylogenetically the newest. It is associated with behavior, analysis of the external environment, instincts and also cognitive abilities. The more complex the functions, the more important is their meaning. (for example, in fish -...., dogs -....) Each hemisphere has a motor zone and a sensory zone. Functionally are divided into regions, for example, visual area, auditory area, speech area (Broca’s and Wernicke’s area) Lower developed animals do not have strict localization of functional zones. An example of brain injury and survival in species of different developmental levels is intended. Fish, amphibians survive and live even after severe brain injuries, higher developed ones can die if the higher parts of the CNS are injured. Basal ganglia The basal ganglia are a group of structures found deep within the cerebral hemispheres. The structures generally included in the basal ganglia are the caudate, putamen, and globus pallidus in the cerebrum, the substantia nigra in the midbrain, and the subthalamic nucleus in the diencephalon. The separate nuclei of the basal ganglia all have extensive roles of their own in the brain, but they also are interconnected with one another to form a network that is thought to be involved in a variety of cognitive, emotional, and movement-related functions. The basal ganglia are best-known, however, for their role https://en.wikipedia.org/wiki/Basal_ganglia in movement. One popular hypothesis suggests that the basal ganglia act to facilitate desired movements and inhibit unwanted and/or competing movements. The brain stem The brainstem is the part of the brain that connects the cerebrum with the spinal cord. the brainstem is an extremely important part of the brain, as the nerve connections from the motor and sensory systems of the cortex pass through it to communicate with the peripheral nervous system. The 3 components of the brain stem are: 1) Medulla oblongata, 2) Pons, 3) Midbrain + reticular formation https://doctorlib.info/anatomy/textbook-clinical- Reticular formation (activating system of the brain) a diffuse neuroanatomy/19.html region of gray matter throughout the brain stem. It is responsible for the non-specific functions of the CNS. Reticular formation is located in the central part of the brain stem. 43  Diseases of the brainstem can result in abnormalities in cranial nerve function, leading to visual and hearing disturbances, changes in sensation, muscle weakness, vertigo, coordination problems, swallowing and speech difficulty, and voice changes. Medulla oblongata Performs two basic functions: 1.Conduction function is associated with nerve fibers: Afferent (ascending) nerve fibers →spinal cord → medulla oblongata → cerebral cortex Efferent (descending) nerve fibers → cerebral cortex → medulla oblongata → spinal cord → effector 2. Reflex functions. Unconditioned reflexes!!!! Nerve centers in medulla oblongata: https://braininjuryhelp.com/brainstem-brain-stem-and- 1. Centers important for life support: cardiac, cerebellum/ respiratory center 2. Defense reflexes: inborn defense reflexes 3. Gastrointestinal centers – 1) food intake (motor); 2) gastric juice secretion centres (secretory); 4. Centers that regulate skeletal muscle tone. (e.g., static and statokinetic reflexes (body posture); reflexes related to the face and scalp muscles (facial expressions)) Midbrain Functions: 1) Primary vision center, which provides visual orienting reflexes – turning the head towards a bright light, eyeball movements, eye accomodation and pupillary responses. The intregration center of this reflex is superior colliculus 2) Primary auditory center that provides auditory orienting reflex - turing ears, head in the direction of a loud sound. midbrain The principal nucleus of the easynotecards.com/notecard_set/91739 auditory pathway is inferior colliculus 3) Centers in the red nucleus regulate and coordinate flexor and extensor tone. If there is an https://slideplayer.com/slide/11439824/ injury between the red nucleus and medulla oblongata, decerebrate rigidity occurs (for example., animal cannot bend legs – they are stretched). 4) In midbrain, the substantia nigra contains centers that https://www.slideserve.com/sook/brain-stem participate in the regulation of very precise, complicated movements E.g., chewing, swallowing, finger movements in humans and primates. 44  Pons Functions: Conduction pathway between higher and lower brain centers Relays signals from forebrain to cerebellum Helps coordinating respiration (regulates the change from inspiration to expiration (the pneumotaxic center)), https://neuroscientificallychallenged.com/po swallowing, bladder control, hearing, equilibrium, eye sts/know-your-brain-pons movement, posture Diencephalon Diencephalon is localized above the midbrain. Consists of 2 main structures: Thalamus (thalami optici) (left and right) Hypothalamus + epithalamus https://en.wikipedia.org/wiki/Diencephalon Thalamus Thalamus is a connection place for all sensory pathways. It combines a wide range of sensory information and projects it to the centers of the CNS by stimulating them Coordinates autonomic and somatic response reaction. Motor pathways go through the thalamus from the subcortical centers to the cerebral cortex Thalamus is like a gate through which all the information from the receptors enters the hemisphere cortex, thus all the afferent impulses. Thereby, thalamus is associated with human and animal senses. https://en.m.wikipedia.org/wiki/Subthalamic_fasciculus Hypothalamus Participates in complex motor reactions, is responsible for the cooperation of autonomic and somatic nervous system !!!! Functions: 1. The main center for the regulation of autonomic functions, because it combines neural and humoral regulation of the body. (coordinates autonomic functions) 2. In the posterior nuclei, the highest subcortical centers of the sympathetic https://www.studocu.com/ph/document/university-of-perpetual-help-system- dalta/anatomy-and-physiology/hypothalamus-and-pituitary-gland/30587392 nervous system are located, in the anterior nuclei – the highest subcortical centers of the parasympathetic nervous system. 45  3. Centers of hunger and satiety (regulation of body weight, food intake) (ventromedial nucleus) 4. Osmotic pressure regulation centers (osmolarity centers). Nucleus supraopticus contains cells with osmoreceptors that regulate the water balance in the body’s internal environment. 5. Sleep-wake regulation. While awake, the reticular formation is active → activates the cerebral cortex → the sleep center is suppressed. When the activity of the reticular formation disappears → the sleep center is not suppressed → we fall asleep. (Tuberomammillary nucleus) 6. Thermoregulation function – central thermoreceptors direct information both to the brain and to the body. (Preoptic and Anterior nuclei) 7. Regulatory centers of reproductive functions and sexual behavior. Regulated through the autonomic nervous system, adenohypophysis and gonads. (Medial preoptic nucleus) Regulation of milk secretion (oxytocin) (Paraventricular and Supraoptic nuclei) 8. Formation of stress induced reactions, including coordination of defense centers (attack, escape, defense…). (Posterior nucleus) 9. Regulation of circadian processes – i.e., regulation of the circadian rhythm (day and night), carried out with the epiphysis (melatonin). (Suprachiamatic nucleus) 10. Formation of emotional behavior (through the sympathetic nervous system) (Dorsomedial nucleus) In HYPOTHALAMUS takes place synthesis of neurohormones24 and their secretion to the hypophysis (pituitary gland) by neural and humoral transport: There are neuroendocrine cells in the anterior part of hypothalamus – nucleus supraopticus and nucleus paraventricularis, which secrete: vasopressin (antidiuretic hormone) and oxytocin. They are transported via the hypothalamo- hypophyseal tract to the NEUROHYPOPHYSIS (posterior lobe of the hypophysis) – neural transport!!! The neurosecretory cells of the middle part of the hypothalamus secrete hypothalamic hypophysiotropic hormones: liberins and statins. They enter the blood capillaries and go to the ADENOHYPOPHYSIS (anterior lobe of the hypophysis) – humoral transport!!! Epithalamus Produces melatonin signaling nighttime sleep Connects the limbic system to other parts of the brain https://www.quora.com/Where-is- the-epithalamus-located 24 A neurohormone is any hormone produced and released by neuroendocrine cells (also called neurosecretory cells) into the blood. 46  Cerebellum Dividied into phylogenetically two distinct parts: * the oldest is involved in balance adjustment, * the newest – coordination of muscle activity; There are nerve centers that regulate movement accuracy, force, direction, amplitude (monitors, modifies). The primary function of the cerebellum is to maintain posture and balance. When we jump to the side, reach forward, or turn suddenly, it subconsciously evaluates each movement. The cerebellum then sends https://leisurecommando.com/body- signals to the cerebrum, indicating muscle movements that will adjust parts-the-feline-brain/ our position to keep us steady. For example, these centers are especially well developed in birds and in those mammals that need to perform quick and precise movements. Participates in the regulation of voluntary and involuntary movements The nerves that coordinate muscle movements, regulate the body’s balance. Regulates skeletal muscle tone and trophic function. If the cerebellum is injured, or removed, then occurs: atony – loss of skeletal muscle tone asthenia25 – physical weakness astasia abasia26 – animal is shaking, swinging ataxia – impaired coordination of movements Higher nervous activity Higher Nervous Activity is the activity of the higher centers of the central nervous system of animals and man “which ensures the normal and complex relations between the entire organism and the external environment” (Pavlov) Associated with the activity of the cerebral cortex and subcortex. The operation of the higher nervous system is based on three principles: The principle of determinism, which means – to condition. i.e., an impulse, appropriate conditions, or a cause for every given action or effect of the higher nervous system has a cause (cause-and-effect) The principle of analysis and synthesis – i.e., the initial decomposition of the whole into its parts or units, and then the gradual reconstruction of the whole from these units or elements (animals evaluate the appearance of food, its smell, taste and only then make a decide to eat or not to eat). The principle of structure – the material substrate of nervous activity is the speed of excitation and inhibition to provide a response (interconnection of the brain structures and functions). The action of higher nervous activity is based on conditioned reflexes. A conditioned reflex is a reaction that the body acquires during its life and responds to the stimulation of receptor. In humans and higher animals, conditioned reflexes are developed through the formation of temporary connections in the cerebral cortex and serve as mechanisms for adaption to the complex changing environmental conditions. Conditioned reflexes are the basic physiological mechanism for higher nervous activity. 25 Asthenia is an condition characterized by generalized weakness and usually involving mental and physical fatigue. 26 Astasia-abasia refers to the inability to either stand or walk in a normal manner. 47  Limbic system (LS) The limbic system is the part of the brain involved in our behavioural and emotional responses, especially when it comes to behaviours we need for survival: feeding, reproduction and caring for our young, and fight or flight responses. The LS is the part of the brain that is the boundary between the old and the new cortex, because by the development, cortex of cerebral hemispheres is divided into the new and the old. The LS https://fitnash.co.uk/limbic-reactions/ https://neuroscientificallychallenged. connects the cortical area and the subcortical formations in com/posts/know-your-brain- different structures. amygdala The LS consists of: 1. Limbic cortex 2. Hippocampus Major structures 3. Amygdala 4. Thalamus: anterior nucleus (n. anterior thalami) and mediodorsal nucleus (n. mediodorsalis thalami) 5. Hypothalamus 6. Septal area 7. Basal ganglia The LS forms a close communication with the hypothalamus and reticular formation. Limbic system (LS) The LS contains: The most active pleasure and wellness centers, in which opioid peptide receptors are naturally located The „brain of the internal organs”, which is responsible for the homeostasis of the internal environment The LS is very closely related to the reticular formation The LS structures are responsible for emotions, instincts Drugs (narcotic substances), their effects – it should be noted that the neurotransmitter of the limbic system is serotonin. Some narcotic substances are structurally very similar to serotonin, and occupy the serotonin place in brain during narcotic intoxication. Morphine molecule is able to bind directly to the opioid peptide receptors, which are the natural centers of pleasure and wellness. They suppress the LS “brain of the internal organs”, then the impulses “mix roads” and disorganize the psyche. Hippocampus (sea horse) There are two hippocampi, located in each hemisphere of the brain. They are seahorse-shaped and are structures mainly associated as being the memory centres of our https://en.wikipedia.org/wiki/Hippocampus brains. The hippocampus is also known as a site where neurogenesis occurs – this means https://www.simplypsychology.org/anatomy-of- that new nerve cells are made here from adult stem cells. the-brain.html Maintains close communication with the entire limbic system, as well as with other brain structures Is involved in orientation and alertness reflex (increased focus on learing dynamics), and in the development of conditioned reflexes. In the hippocampus, microstructural changes occur continuously, dendrites quickly form new branches (filopodia) and new synapses are formed; new formations can quickly disappear and form again. 48  Amygdala The amygdala is an almond-shaped structure, located right next to the hippocampus. Functions: emotional responses, including feelings of happiness, fear, anger, and anxiety formation of new memories has a role in how memorable memories can be linked with the fight-or-flight response, as stimulating activity in the amygdala can influence the body’s automatic fear response Damage to the Limbic System Amygdala damage can result in more aggression, irritability, loss of control of emotions, and deficits in recognizing emotions, especially recognizing fear. Damage to the hippocampus could lead to deficits in being able to learn anything new, as well as affecting memory. Hypothalamus damage can affect the production of certain hormones, including those which can affect mood and emotion. Uncontrolled emotions – more aggression, anxiety, and agitation. Olfactory impairments Memory impairments Abnormal biological rhythms Depression Reticular formation or reticular activating system (RAS) The reticular formation is a set of interconnected nuclei that are located throughout the brainstem. Histologically, RAS looks like a network. Has an activating and depressing effect on the CNS (there is a sleep center) ! The RF is very sensitive to chemicals, especially barbiturates (sleep medicine), other medications, hormones. ! In anesthesia, the RF is the first structure that stops functioning ! Damage of the RF can cause lethargic sleep. The main functions of RAS RAS implements nonspecific functions of CNS https://integratedlistening.com/blog/meet-the- (receives information, processes the information and transmits it to other reticular-activating-system-ras/ regions of the brain) Affects the level of excitation and activity of the other parts of the CNS. Neural network-like structure of the RAS provides connection to specific conduction ways (alertness, tone, voluntary, involuntary motor skills, etc.) Convergence of sensory information takes place in the RAS by “erasing” the specificity of sensory information (different irritants – same activation) The activity of the RAS itself is maintained by impulses from: sensory, viscerosensory neurons, cerebellum, thalamus, cerebral cortex. 49