BIO329 Exam 2 PDF

BIO 329 EXAM 2 – CH. 5, 6, 7 Synapses Electrical synapse Electrical PSP: A continuations of the energy in a post synaptic cell, will its reach threshold? Synchronistic/asynchronies in action potential and oscillations à gap junctions Gap junctions - - Channel o Connexons -formed by six connexins form the gap junctions o Proteins that span membranes Cells said to be “electrically coupled.” o Flow of ions from cytoplasm of one cell to cytoplasm of another cell Electrical Synapses - Unlike most chemical synapse, bidirectional; Very fast transmission - o Postsynaptic potentials (PSPs) Synaptic integration: several PSPs occurring simultaneously to excite a neuron (causes AP) Chemical synapses (more predominant) - Mitochondria is towards the end of the synapse because it needs a lot of energy to packed into the secretory granules Axodendritic: axon and dendrite Axosomatic: axon to cell body Axoaxonic: axon to axon Axospinous: axon to dendritic spine Dendrodentritic: Dendrite to dendrite Two categories of CNS Synaptic membrane di7erentiations - Gray’s type I: asymmetrical, usually excitatory - Gray’s type II: symmetrical, usually inhibitory The Neuromuscular Junction - The synapse connection between a motor neuron and a muscle Neurotransmitter categories - Neurotransmitter synthesis and Storage à textbook Release of NT by exocytosis à Textbook NT mechanisms od release +NT recpetors - Process of exocytosis stimulated by intracellular calcium (Ca2+) Proteins alter conformation activated. Vesicle membrane incorporated into presynaptic membrane. Neurotransmitter released into cleft. Vesicle membrane recovered by endocytosis. Excitatory and inhibitory Post-synaptic Potentials - EPSP: transient postsynaptic membrane depolarization caused by presynaptic release of neurotransmitter. IPSP: transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter. Autorecpeptors - Receptors commonly found in membrane of presynaptic axon terminal. Presynaptic receptors sensitive to the neurotransmitter released by the presynaptic terminal called auto receptors. Consequences of activating auto receptors vary— common e[ect is inhibition of neurotransmitter release. Appear to function as a sort of safety valve. Neurotransmitter recover and degradation - Di[usion of transmitter molecules away from the synapse Reuptake: Neurotransmitter reenters presynaptic axon terminal. Enzymatic destruction inside terminal cytosol or synaptic cleft Desensitization: for example, AChE cleaves Ach to render it inactive. Neuropharmacology - Receptor antagonists: inhibitors of neurotransmitter receptors Example: curare Receptor agonists: mimic actions of naturally occurring neurotransmitters. Example: nicotine Defective neurotransmission: root cause of neurological and psychiatric disorders Synaptic Integration - Process by which multiple synaptic potentials combine within one postsynaptic neuron Most CNS neurons receive thousands of synaptic inputs. Neural computation Quantal analysis of EPSPs Synaptic vesicles: elementary units of synaptic transmission - - Quantum: an indivisible unit Miniature postsynaptic potential (“mini”) Quantal analysis: used to determine number of vesicles that release during neurotransmission. o Example: at neuromuscular junction, about 200 synaptic vesicles—EPSP of 40 mV or more At many CNS synapses, a single vesicle— EPSP of few tenths of a millivolt EPSP summation: - Allows for neurons to perform sophisticated computations. Integration: EPSPs added together to produce signiﬁcant postsynaptic depolarization Spatial summation: EPSPs generated simultaneously at di[erent sites. Temporal summation: EPSPs generated at same synapse in rapid succession. Brain Stem à responsible for important functions such as breathing, consciousness, blood pressure, heart rate, and sleep. Prefrontal Cortex à responsible for regulating thoughts, actions, and emotions through connections to other parts of the brain. Motor Cortex à located in the frontal lobe, generate signals to direct voluntary movements of the body, it consists of the primary motor cortex, premotor cortex, and the supplementary motor area. Primary Visual Cortex à located in the occipital lobe, responsible for receiving and integrating visual information and send to other regions of the brain. Ventricles à The ventricles store and produce cerebrospinal ﬂuid (CSF) and are responsible for keeping the CSF moving. Cerebellum à The cerebellum helps improve motor skills in individuals by detecting errors in movements and adjusting the next movement, which strengthens the connections from the brain to the body. Corpus Callosum à consists of white mater tracts that connect the left and right cerebral hemispheres. Basal Ganglia à The basal ganglia is responsible for motor control, motor learning, executive functions, behaviors and emotions. Thalamus à Relays information about the body’s senses to the rest of the brain. Responsible for vision, hearing, touch, proprioception, and taste signals Hypothalamus à The hypothalamus provides a link between the central nervous system and the endocrine system, controls the pituitary gland, regulates body temperature, and hunger, thirst, sleep, mood and release of hormones from the pituitary gland. Hippocampusà Responsible for long term memory, it communicates with the rest of the brain using the entorhinal cortex. Cranial Nerves à there are 12 cranial nerves in the body and they connect the brain to other parts of the face, neck and body. Every year, thousands of people in the US su[er from some type of traumatic brain injury (TBI) due to accidents such as motor vehicles accidents, sports accidents, and war injuries. A traumatic injury to the brain may cause handicaps in various aspects of a person’s life, and therefore it is very critical that TBI be identiﬁed and intervention be presented to the patients as quickly as possible. Regardless of the severity of the injury (mild, moderate or severe) an important step is to identify the extent of the injury. As soon as a traumatic brain injury patient is brought to the hospital, the doctors typically have the patient get a head CT (computerized tomography) scan. CT has become a vital tool in the assessment of patients with serious head injury and has enabled much better quality in management of TBI. CT scans can show the bleeding, swelling, or pressure in the brain, fractures in the skull, as well as other structural abnormalities that may be caused by a traumatic injury. Looking at a CT scan, physicians can determine the best course of action and discuss about the functional di[iculties that the patient may have after the accident as suggested by the locations of the injury in the brain. Case Study A signiﬁcant event occurred that altered Taylor’s cognitive abilities signiﬁcantly. Taylor’s family was in a motor vehicle accident. When their car was hit by another car, Taylor hit the back of her head to her seat and she was catapulted from the back seat to the windshield. They were brought to the emergency room 20 minutes after the accident. Taylor was unconscious when she was brought to the hospital. Taylor was immediately given a CT scan. CT Scan Results: When the doctor looked at Taylor’s CT image, he saw the following signs of an epidural hematoma: There was a high-density collection of blood (appears white on a CT) between the brain and the inner layer of the skull, biconvex, lens shaped. The build-up of blood was in the epidural space of the head, which is between the dura mater (the outer membrane of the brain) and the skull. Q: As Taylor’s physician, what action can you / should you take clinically? And what is the expected outcome? Taylors physician should try to remove the blood from the brain by draining it or surgically remove the part of the skull to remove the hematoma. An epidural hematoma can be fatal if not treated quickly and e;iciently, and even if it is some disabilities many occur. Synaptic transmission - Information transfer at as synapse Plays roles in all the operations of the nervous system Chemical and electrical Directions of information flow - Generally, in one direction: neuron to target cell First neuron: presynaptic neuron Target cell: post synaptic neuron Electrical vs chemical synapses During a chemical synapse the information is transferred via the release of a NT from one cell that is detected by an adjacent cell During an electrical synapse the cytoplasm of adjacent cells are directly connected by clusters of intercellular channels called gap junctions. Synaptic integration: several PSPs occurring simultaneously to excite a neuron. Axodendritic: axon and dendrite Axosomatic: axon to cell body Axoaxonic: axon to axon Axospinous: axon to dendritic spine Dendrodentritic: Dendrite to dendrite Neurotransmitter categories Amino acids: small organic molecules-vesicles - Examples: glutamate (excitatory), glycine (inhibitory), GABA (inhibitory) Amines: small organic molecules -vesicles - Example: dopamine, acetylcholine Peptides: short amino acid chains -secretory granules Examples: dynorphin, enkephalins EPSP: transient postsynaptic membrane depolarization caused by presynaptic release of neurotransmitter. Generation of EPSP: occurs when sodium channels open in response to stimulus. The electrochemical gradient drives sodium to rush into the cell. When sodium brings its positive charge into the cell, the cells membrane potential becomes more positive or depolarizes. IPSP: Transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter. Generation of IPSP: when the inhibitory presynaptic cell gets connected to the dendrite and ﬁres an action potential. Why would brain synapses use chemical transmission? à Chemical synapse are unidirectional- they limit information from presynaptic to postsynaptic cell. Along an axon, AP can propagate in either direction. Information ﬂow within the nervous system can be directed from input to output using chemical synapses, at which only the presynaptic terminal releases neurotransmitter, and only the postsynaptic membrane contains receptors. What is meant by quantal release of neurotransmitter? à quantal release of NT refers to the process by which NT are released from synaptic vesicles into the synaptic cleft in discrete packets known as quanta. These quanta are pre-packaged amounts of NT molecules within synaptic vesicles. When an AP reaches the presynaptic terminal of a neuron, it triggers the opening of voltage-gated calcium channels, leading to an inﬂux of calcium ions inti the terminal. The increase in calcium concentration inside the terminal causes synaptic vesicles containing NT molecules to fuse with the presynaptic membrane and release their contents into the synaptic cleft. GABA-gated ion channel that is permeable to Cl-. GABA also activates a G-protein-coupled receptor called the GABA-B receptor, which cause potassium-selective channels to open. What e[ect would GABAb receptor activation have on the membrane potential? à Activation of GABA-B receptors typically leads to the opening of Potassium-selective channels. Potassium ions have a higher concentration inside the cell compared to the outside, and their e[lux tends to hyperpolarize the membrane potential, making it more negative. This is due to K+ ions moving out of the cell, following their concentration gradient. Agonist: drug or compound that binds to a receptor and activates it mimicking the cation of endogenous ligands Antagonist: Drug or compound that binds to a receptor but does not activate it. Instead, it blocks the receptor from being activated by endogenous ligands or other agonists. Quanta MEPP Three criteria for NT: - Synthesis and storage in presynaptic neuron Released by presynaptic axon terminal. When applied, mimics postsynaptic cell response produced by release of neurotransmitter from the presynaptic neuron. Immunocytochemistry: localize molecules to cells, used to anatomically visualize the localization of a speciﬁc protein or antigen in cells by use of a speciﬁc primary antibody that binds to it. Studying transmitter release: - Transmitter candidate: synthesized and localized in terminal and released upon stimulation CNS contains a diverse mixture of synapses that use di[erent transmitters. Studying synaptic mimicry - Qualifying condition: molecules evoke same response as NT. Microtophoresis: assess post synaptic actions. Microelectrode: measure e[ects on membrane potential Involves inserting a double micropipette close to a nerve cell in the brain. An ionized ﬂuid is injected through one barrel of the pipette, while a concentrated saline solution in the other tube serves as an electrical conductor to detect and transmit any changes in neural activity to an oscilloscope. Studying receptors - - Ligand binding methods o Identify natural receptors using radioactive ligands. o Ligands can be agonist, antagonist, or chemical NT. o Example: opioid receptors Molecular anaylsis – receptor protein classes Acetyl CoA + Choline à Ach + CoA Ach à Acetic acid+Choline Neurotransmitters à Transmit information between neurons, essential link between neurons and e[ector cells. Signaling pathways à signaling network within a neuron somewhat resembles brains neural network, inputs vary temporarily and spatially to increase and/or decrease drive, delicately balances, signals regulat signals – drugs can shift the balance and signaling power. Peripheral nervous system à nervous system outside the brain and spinal cord - Somatic PNS: Innervates skin, joints, muscles. Dorsal root ganglia: clusters of neuronal cell bodies outside the spinal cord that contain somatic sensory axons. Visceral PNS: innervates internal organs, blood vessels, glands. Excitatory - - Depolarize the postsynaptic membrane, making it more likely for the postsynaptic neuron to generate an action potential. This depolarization usually occurs by allowing positively charged ions such as sodium or calcium, to enter the post synaptic neuron, bringing its membrane potential closer to the threshold for ﬁring an action potential. Excitatory neurotransmitters facilitate the transmission of nerve impulses along neural circuits and are involved in processes such as sensory perception, motor control, and cognitive functions. Inhibitory - - Hyperpolarize the postsynaptic membrane, making it less likely for the postsynaptic neuron to generation action potential This hyperpolarization typically occurs by allowing negatively charged ions such as chloride or potassium to enter or exit the postsynaptic neuron, moving it membrane potential further away from the threshold for ﬁring an action potential Inhibitory neurotransmitters help regulate neuronal excitability and prevent excessive neural activity, contributing to process such as maintaining resting membrane potential, controlling motor output, and modulating sensory input. Basic GPCR structure CNS di[erentiation Neural tube defects Spina biﬁda principles Spina biﬁda is a congenital condition characterized by the incomplete closure of the neural tube during embryonic development. The neural tube is the embryonic structure that eventually develops into the brain and spinal cord. When the neural tube fails to close completely, it can result in various types of spina biﬁda. The basic principles of spina biﬁda include: 1. Incomplete Closure of the Neural Tube: During early embryonic development, the neural tube forms and closes to create the central nervous system. In spina biﬁda, this closure is incomplete, leading to a gap or opening in the spinal column. 2. Types of Spina Biﬁda: - Spina Biﬁda Occulta: This is the mildest form, where one or more vertebrae do not close properly, but the spinal cord and meninges (protective coverings of the spinal cord) remain within the spinal canal. It may not cause any symptoms and may go unnoticed. - Meningocele: In this type, the meninges protrude through the opening in the vertebrae, forming a sac ﬁlled with cerebrospinal ﬂuid. However, the spinal cord remains intact and does not protrude through the opening. - Myelomeningocele: This is the most severe form, where both the meninges and the spinal cord protrude through the opening in the vertebrae, forming a sac outside the body. This can lead to signiﬁcant neurological complications and disabilities. 3. Potential Complications: - Neurological Deﬁcits: Myelomeningocele can cause paralysis, weakness, or loss of sensation below the level of the spinal cord defect. - Hydrocephalus: Some individuals with myelomeningocele also develop hydrocephalus, a condition characterized by an accumulation of cerebrospinal ﬂuid in the brain, which can lead to increased pressure within the skull. - Bladder and Bowel Dysfunction: Spina biﬁda can a[ect the nerves that control bladder and bowel function, leading to urinary and fecal incontinence. - Orthopedic Issues: Individuals with spina biﬁda may develop orthopedic problems such as scoliosis (curvature of the spine) or clubfoot due to muscle weakness and imbalance. 4. Multidisciplinary Management: Management of spina biﬁda typically involves a multidisciplinary approach, including pediatric neurosurgery, orthopedics, urology, physical therapy, occupational therapy, and other specialists. Treatment may involve surgical repair of the spinal defect, management of associated complications, and ongoing rehabilitation and support to optimize function and quality of life. Overall, the basic principles of spina biﬁda revolve around the incomplete closure of the neural tube during embryonic development, leading to a range of potential neurological and physical complications that require comprehensive management and support. CNS neuroanatomy- function relationships Major neuroimaging techniques, orientations, applications Computed Tomography (CT) - Generates an image of a brain slice X-ray beams used to generate data for a digitally reconstructed image Magnetic resonance imaging (MRI) - Based on how hydrogen atoms respond in the brain to perturbations of a strong magnetic ﬁeld Signals mapped by computer to create imagery MRI vs CT - MRI is in more detail, does not require X-irradiation, brain slice image in any angle Positron emission tomography (PET) Functional MRI (fMRI) Basic principles: - Detect changes in regional blood ﬂow and metabolism within the brain Active neurons demand more glucose and oxygen, thus more blood to active regions Techniques detect changes in blood ﬂow Common features of cerebral cortex in vertebrates à cell bodies in layers or sheets, surface layer separated from pia mater, layer I, apical dendrites form multiple branches. Name the three main parts of the hindbrain à The three main parts of the hindbrain are the cerebellum, the pons, and the medulla oblongata. The cerebellum and pons develop from the rostral half of the hindbrain and the medulla develops from the caudal half. The pons and medulla are part of the brain stem. What is the fate of tissues derived from the embryonic neural tube? Neural crest? à the entire central nervous system (CNS) develops from the walls of the neural tube, which is initially only a thin sheet of ectoderm that deepens to form a neural groove with folds that fuse to form the neural tube. On either side of the neural tube are pockets of neuronal precursors called neural; crest cells. The entire PNS develops from these neural crest cells. Where is the CSF produced? à The choroid plexus in the lateral ventricles of the cerebral hemispheres produces CSF. What path does the CSF take before it is absorbed in the bloodstream? à The CSF ﬂows from the paired lateral ventricles through unpaired ventricles in the thalamus, midbrain, and brain stem as well as the spinal canal. Speciﬁcally CSF ﬂows through the cerebral aqueduct into the fourth ventricle. CSF also surround the outside of the brain. CSF exits the ventricular system vis the subarachnoid space through small apertures near the base of the cerebellum. Is the myelin sheath of optic nerve axons provided by Schwann cells or oligodendroglia? à The retina and optic nerve are part of the CNS, so the we know that oligodendroglia provide myelin for the CNS and Schwann cells provide myelin for the PNS. Neurotransmitter types: ` Ach Precursors: acetyl-CoA and choline Enzyme: Choline acetyltransferase Types of channels activated by Ach: Nicotinic Acetylcholine receptor (AChR) Typical action of Ach: excitatory How is Ach action terminated: Acetylcholinesterase (enzyme that hydrolyzes Ach in the synaptic cleft Glutamate Precursors: Glutamine Enzyme: Glutaminase Types of channels activated by Glutamate: Glutamate-dependent ion channels (AMPA/NMDA) Typical action of glutamate: Excitatory How is Glutamate action terminated: uptake into presynaptic neuron and surrounding glia Glycine Precursor: serine Enzyme: serine transhydroxymehylase Types of channels activated by glycine: Glycine-activated channels Typical action of glycine: Inhibitory How is glycine action terminated: Uptake into presynaptic neuron and surrounding glia GABA Precursor: glutamate Enzyme: Glutamic acid decarboxylase (pyridoxal phosphate needed as cofactor) Types of channel activated by GABA: GABA-A channels Typical action of GABA: Inhibitory How is GABA action terminated: Uptake into presynaptic neuron and surrounding glia Describe the proteins involved in a GPCR-couple pathway that results in activation of PKA. What steps are there? What activates and inactivates each step in the pathway? 1. Ligand binds to GPCR, activating it. Among mechanisms to stop activated receptor: Ligand dissociation 2. Activated GPCR activates G-protein, facilitating nucleotide exchange on alpha subunit. GDP dissociate, GTP associates. 3. Nucleotide exchange on alpha subunit results in dissociation of G-alpha-GTP from G-beta/G-gamma. 4. G-alpha-GTP binds to and activates e[ector enzyme adenylyl cyclase. Adenylyl cyclase activity terminated when G-alpha hydrolyzes GTP to GDP + inorganic phosphate. 5. Activated Adenylyl cyclase catalyzes the creation of cAMP from substrate ATP. Consider a single molecule of GTP. Describe where this Guanine base enters and exits the G-protein cycle. Describe where the terminal phosphate of GTP enters and exits the cycle. 1. Molecular of GTP binds to G-alpha that has been activated by GPCR (and so has released GTP) 2. G-alpha-GTP dissociates from G-beta/G-gamma and binds to e[ector enzyme. 3. Molecule of GTP on G-alpha is hydrolyzed by G-alpha and loses its terminal phosphate, resulting in GDP, which continues to be bound by G-alpha. 4. G-alpha-GDP dissociates from e[ector enzyme and rebinds G-beta/G-gamma 5. G-alpha-GDP/G-beta/G-gamma complex binds to GPCR.

Document Details

Tags

Related

Summary

Full Transcript