Neural Transmission Exam Notes PDF

NEURAL TRANSMISSION  Neural Transmission Chemical synapses Electrical synapses  EPSPs and IPSPs EPSP: transient postsynaptic membrane depolarization caused by presynaptic release of neurotransmitter IPSP: transient hyperpolarization of postsynaptic membrane potenti...

NEURAL TRANSMISSION  Neural Transmission Chemical synapses Electrical synapses  EPSPs and IPSPs EPSP: transient postsynaptic membrane depolarization caused by presynaptic release of neurotransmitter IPSP: transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter The Major Chemical Neurotransmitters Diffuse Modulatory Systems Gap Junctions  Gap Junctions - Connexon channel - formed by six connexins - Cells are “electrically coupled” - ions flow from cytoplasm of one cell to another cell - Unlike most chemical synapses, bidirectional - Very fast transmission - Synaptic integration: several postsynaptic potentials (PSPs) occurring simultaneously to excite a neuron (causes AP) Gap Junctions  Chemical Synapses Axodendritic: axon to dendrite Axosomatic: axon to cell body Axoaxonic: axon to axon Axospinous: axon to dendritic spine Dendrodendritic: dendrite to dendrite Chemical Synapses Three Dimensional Electron Microscopy  Principles of Chemical Synaptic Transmission Neurotransmitter synthesis Load neurotransmitter into synaptic vesicles Vesicles fuse to presynaptic terminal Neurotransmitter spills into synaptic cleft Binds to postsynaptic receptors Biochemical/electrical response elicited in postsynaptic cell Removal of neurotransmitter from synaptic cleft Neuromuscular junction PRESYNAPTIC NEURON - Motor neuron action potential (~2msec) - Acetylcholine release - 200 synaptic vesicles MUSCLE - Acetylcholine (nicotinic) receptors - 2 ACh molecules/receptor - End-plate potential (40+mV) - Muscle action potential (Na+/K+) - ~5msec in duration - Muscle contraction Action Potentials in Neurons and Muscle Tissues  Postsynaptic Potentials CNS vs NMJ A single vesicle ~200 vesicles EPSP/Glutamate EPP/ACh ~0.5mV ~40+mV  The Major Neurotransmitters Other: Gases: Lipid soluble: Adenosine and ATP NO and CO Endocannabinoids Peptide Synthesis, Transport, and Release Vesicle Exocytosis  Calcium and Vesicle Exocytosis Calcium-sensitive dye at rest and during a train of action potentials (Llinas, etal.)  Calcium and Vesicle Exocytosis Process of exocytosis stimulated by intracellular calcium [Ca2+]i Proteins alter conformation—activated Vesicle membrane incorporated into presynaptic membrane Neurotransmitter released into cleft Vesicle membrane recovered by endocytosis Exocytosis and Endocytosis  Neurotransmitter Receptors Transmitter-gated ion channels Neurotransmitters: Glutamate vs GABA  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 Neurotransmitter Life Cycle - Acetylcholine  Bacteria, Spiders, Snakes, and People BACTERIA: - Clostridium botulinum (botulinum neurotoxins) - Blockade of neuromuscular Acetylcholine release - SNARE protein target MEDICINE: - Botox injections to treat migraine pain (FDA) - Muscle spasms BEAUTY: - Facial wrinkles (Botox party) Bacteria, Spiders, Snakes, and People  Bacteria, Spiders, Snakes, and People BLACK WIDOW SPIDER: - Venom with latrotoxin - Protein molecule - Punctures cells & depletes Ca2+ - Can facilitate NT release without Ca2+ TAIWANESE COBRA - Alpha-bungarotoxin - Postsynaptic Ach receptor (desensitization) - Respiratory muscle paralysis  Bacteria, Spiders, Snakes, and People Organophosphates - Sarin Gas (chemical weapon) - AChe irreversible inhibitor - Overabundance of ACh - AChR (receptor) desensitization (Ache cleaves ACh to render it inactive) - Parathion (insecticide) – toxic in high doses PHARMACEUTICALS - Cholinesterase inhibitors (CINs) - Alzheimer’s medications  Neuropharmacology Study of effects of drugs on nervous system tissue 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  Autoreceptors Receptors commonly found in membrane of presynaptic axon terminal Presynaptic receptors sensitive to the neurotransmitter released by the presynaptic terminal called autoreceptors Consequences of activating autoreceptors vary—common effect is inhibition of neurotransmitter release. Appear to function as a sort of safety valve Negative feedback mechanism G-Protein-Coupled Receptor  Synaptic Integration Process by which multiple synaptic potentials combine within one postsynaptic neuron Most CNS neurons receive thousands of synaptic inputs (E and I). Neural computation  EPSP Summation Integration: EPSPs added together to produce significant postsynaptic depolarization Spatial summation: EPSPs generated simultaneously at different sites Temporal summation: EPSPs generated at same synapse in rapid succession  Decreasing Depolarization along a Long Dendritic Cable Simplified view Dendrite can be viewed as a straight cable. Membrane depolarization falls off exponentially with increasing distance along the cable. Vx = Vo/ex/  Dendritic length constant () In reality, dendrites are very elaborate structures that contribute to more complex integrative properties. Many dendrites have voltage-gated sodium, calcium, and potassium channels. Can act as amplifiers of postsynaptic potentials (vs. passive) Dendritic sodium channels in some cells may carry electrical signals in opposite direction—from soma outward along dendrites.  IPSPs and Shunting Inhibition Synapse inhibits current flow from soma to axon hillock.  Modulation Synaptic transmission that modifies effectiveness of EPSPs generated by other synapses with transmitter-gated ion channels Example: activating NE β receptor  Concluding Remarks Chemical synaptic transmission Rich diversity allows for complex behaviours. Provides explanations for drug effects Defective transmission is the basis for many neurological and psychiatric disorders. Key to understanding the neural basis of learning and memory Chemicals associated with behaviour and disease NEUROTRANSMITTER SYSTEMS  Three Criteria for Neurotransmitters 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 CNS contains a diverse mixture of synapses that use different neurotransmitters. Brain slice as a model. Kept alive in vitro  stimulate synapses, collect and measure released chemicals New methods such as optogenetics  Studying NTs: Immunocytochemistry Localizing transmitters and transmitter-synthesizing enzymes Immunocytochemistry—localize molecules to cells  Studying NTs: In situ hybridization In situ hybridization Localize synthesis of protein or peptide to a cell (detect mRNA)  Studying Synaptic Mimicry Qualifying condition: Molecules evokes same response as neurotransmitter. Microiontophoresis : assess postsynaptic actions Microelectrode: measures effects on membrane potential Uncaging Neurotransmitters https://www.nature.com/articles/nmeth793  Amino Acid Neurotransmitters Glutamate Glycine GABA Glutamic acid decarboxylase (GAD) - Key enzyme in GABA synthesis - Good marker for GABAergic neurons - GABAergic neurons are major source of synaptic inhibition in the CNS.  Amino Acid Receptor Channels: Glutamate Fast synaptic transmission Sensitive detectors of chemicals and voltage Regulate flow of large currents Differentiate between similar ions Glutamate receptors AMPA, NMDA, and kainate Amino Acid Receptor Channels: Glutamate  Amino Acid Receptor Channels: Glutamate Glutamate-gated channels AMPA, NMDA, kainate  Amino Acid Receptor Channels: NMDA Voltage-dependent NMDA channels Coincident detector Synaptic plasticity Nueorlogical disorders Amino Acid Receptor Channels: NMDA Glutamate Life Cycle Amino Acid Receptor Channels: mGluRs https://www.sciencedirect.com/science/article/pii/S1043661816312130?via%3Dihub Amino Acid Receptor Channels: GABAa GABA-gated and glycine-gated channels GABA mediates most synaptic inhibition in CNS. Glycine mediates non-GABA synaptic inhibition. Bind ethanol, benzodiazepines, barbiturates  Amino Acid Receptor Channels: GABAb https://www.sciencedirect.com/science/article/pii/S0959438811000304?via%3Dihub Amino Acid Receptor Channels: GABAa/b Amino Acid Receptor Channels: GABAa/b Amino Acid Receptors Diffuse Modulatory Systems Diffuse Modulatory Systems: Acetylcholine  Diffuse Modulatory Systems: Acetylcholine The shortcut pathway From receptor to G-protein to ion channel—fast and localized Diffuse Modulatory Systems  Diffuse Modulatory Systems: Acetylcholine Basal forebrain complex - Core of telencephalon, medial and ventral to basal ganglia - Function: mostly unknown, participates in learning and memory Pontomesencephalotegmental complex - Utilizes ACh - Function: regulates excitability of thalamic sensory relay nuclei Diffuse Modulatory Systems: Acetylcholine nACh – depolarizing and repolarizing - Na+ in and K+ out mACh – hyperpolarizing - K+ outward only Diffuse Modulatory Systems: Acetylcholine The shortcut pathway From receptor to G-protein to ion channel—fast and localized Diffuse Modulatory Systems: Catecholamines Involved in movement, mood, attention, and visceral function Tyrosine: precursor for three amine neurotransmitters that contain catechol group Dopamine Norepinephrine Epinephrine (adrenaline) Diffuse Modulatory Systems: Dopamine Ventral tegmental area - Innervates circumscribed region of telencephalon - Mesocorticolimbic dopamine system: dopaminergic projection from midbrain Substantia nigra - Axons project to the striatum. - Facilitates the initiation of voluntary movements (degeneration causes Parkinson’s disease) Diffuse Modulatory Systems: Norepinephrine Path: Axons innervate cerebral cortex, thalamus, hypothalamus, olfactory bulb, cerebellum, midbrain, and spinal cord. Function: regulation of attention, arousal, sleep–wake cycles, learning and memory, anxiety and pain, mood, brain metabolism Activation: new, unexpected, nonpainful sensory stimuli  Diffuse Modulatory Systems: Stimulants Stimulants: block catecholamine reuptake Cocaine targets DA reuptake. Amphetamine blocks NE and DA reuptake and stimulates DA release. Diffuse Modulatory Systems: Serotonin (5-HT) Amine neurotransmitter - Derived from tryptophan Regulates mood, emotional behavior, sleep Path: innervate many of the same areas as noradrenergic system Function: together with noradrenergic system, comprise the ascending reticular activating system Particularly involved in sleep–wake cycles, mood  Diffuse Modulatory Systems: Antidepressants Selective serotonin reuptake inhibitors (SSRIs)—antidepressants LSD, Psilocybe mushrooms, and peyote interacts with serotonin signalling. Diffuse Modulatory Systems: Antidepressants  Other Neurotransmitter Candidates and Intercellular Messengers: Adenosine ATP excites some neurons, binds to purinergic receptors. Adenosine (core of ATP) – agonist of Adenosine receptors (AR) Caffeine - competitive antagonist https://www.youtube.com/watch?v=jOfquPE1cnU  Other Neurotransmitter Candidates and Intercellular Messengers: Endocannabinoids Endocannabinoids (pain regulation, appetite, sleep & euphoria) Retrograde messengers/Lipid soluble CB1 – most abundant GPCR Similar to Phytocannabinoids from cannabis Endogenous vs Exogenous Natural vs Synthetic Binding affinity  Studying Receptors Ligand-binding methods Identify natural receptors using radioactive ligands Ligand can be agonist, antagonist, or chemical neurotransmitter. Example: opiate receptors Molecular analysis—receptor protein classes Transmitter-gated ion channels GABA receptors 5 subunits, each made with 6 different subunit polypeptides  G-Protein-Coupled Receptors and Effectors Three steps in transmission Binding of the neurotransmitter to the receptor protein Activation of G-proteins Activation of effector systems Basic structure of G-protein-coupled receptors (GPCRs) Single polypeptide with 7 membrane-spanning alpha-helices  G-Protein-Coupled Receptor Activation Inactive: 3 subunits—, , and — “float” in membrane ( bound to GDP) Active: bumps into activated receptor and exchanges GDP for GTP G-GTP and G—influence effector proteins G inactivates by slowly converting GTP to GDP. G and G recombine to start the cycle again.  G-Protein-Coupled Receptor Activation Push–pull method (different G-proteins stimulate or inhibit adenylyl cyclase) NE alpha vs beta (same agonist)  Second messenger cascades G-protein: couples neurotransmitter with downstream enzyme activation Some cascades branch G-protein activates PLC  generates DAG and IP3  activate different effectors  Phosphorylation and dephosphorylation Phosphate groups added to or removed from a protein Changes conformation and biological activity The function of signal cascades Signal amplification by G-protein-coupled receptors  G-Protein-Coupled Effector Systems Signal amplification  Divergence and Convergence Divergence One transmitter activates more than one receptor subtype  greater postsynaptic response Convergence Different transmitters converge to affect same effector system. The Structure of the Nervous System Mammalian Brains Basic Anatomical References  Meninges Three membranes that surround the brain Dura mater Arachnoid membrane Pia mater  The Ventricular System Ventricles: cerebrospinal fluid (CSF)- filled caverns and canals inside brain Choroid plexus: specialized tissue in ventricles that secretes CSF CSF circulates through ventricles; absorbed in subarachnoid space in sagittal sinus and via lymphatic clearance 150 mL of CSF and 430–530 mL/day produced (adult humans). 99% water, 1% proteins, ions, neurotransmitters, and glucose https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057699/ The Ventricular System  The Peripheral Nervous System 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 The Peripheral Nervous System  Understanding CNS Structure Through Development Ventricular system and the CNS The CNS forms from the walls of a fluid-filled neural tube. The inside of the tube becomes ventricular system. The neural tube - NEURULATION Endoderm, mesoderm, ectoderm Neural plate, neural groove Fusion of neural folds Neural tube (forms CNS neurons) Neural crest (forms PNS neurons) Formation of the Neural Tube  Three Primary Brain Vesicles & Differentiation Differentiation: process by which structures become complex and specialized Retina part of forebrain, not PNS  Differentiation of the Telencephalon & Diencephalon Telencephalon: cerebral hemispheres, olfactory bulbs, basal telencephalon Diencephalon: thalamus and hypothalamus  Major White Matter Systems Axons extend from developing forebrain to other parts of nervous system Cortical white matter Corpus callosum Internal capsule  Thalamus and Cortex Forebrain structure-function relationships Cerebral cortex Analyze sensory input and command motor output Thalamus: gateway to the cortex Axons from thalamus to cortex pass through the internal capsule. Axons carry information from contralateral side of the body. Axons from cortex to thalamus also pass through internal capsule. Hypothalamus controls visceral nervous system.  Differentiation of the Midbrain Midbrain structure-function relationships Contains axons descending from cortex to brain stem and spinal cord Example: corticospinal tract Information conduit from spinal cord to forebrain and vice versa, sensory systems, control of movements Tectum - superior colliculus (receives sensory info from eye), inferior colliculus (receives sensory info from ear) Tegmentum - Substantia nigra (black substance) and red nucleus— control voluntary movement  Cerebellum, Pons, & Midbrain Hindbrain structure-function relationships Cerebellum: movement control Procedural memories Pons: switchboard connecting cerebral cortex to cerebellum Midbrain: Corpora quadrigemina superior (saccadic eye movements) and inferior colliculi (hearing)  Differentiation of the Rostral & Caudal Hindbrains  Motor Cortex & Pyramidal Decussation Corticospinal “Pyramidal” Tract Differentiation of the Spinal Cord Putting the Pieces Together  Special Features of the Human CNS Similarities in rat and human brain Basic arrangement of various structures Differences in rat and human brain Convolutions on human cerebrum surface: sulci and gyri Size of olfactory bulb Growth of cerebral hemisphere: temporal, frontal, parietal, occipital Useful Descriptions Human Brain Human Cerebrum: Brodmann’s areas Human Brain: Medial View  The Limbic System - Cingulate gyrus (emotion experience) - Hippocampus - (memory formation & recall) - Semantic memory - Amygdala (fear response) - Anterior thalamic nucleus (expression of emotional response) - Hypothalamus - Fornix There is not one emotions processing system. The Ventral Surface Major Parts and Functions  A Guide to the Cerebral Cortex Common features of cerebral cortex in vertebrates Cell bodies in layers or sheets Surface layer separated from pia mater, layer I Apical dendrites form multiple branches A Guide to the Cerebral Cortex Neocortical Evolution and Structure-Function Relationships Similar structure across mammals, but …association areas Primary sensory areas, secondary sensory areas, motor areas Association areas of cortex—more recent evolution A Guide to the Diencephalon A Guide to the Cranial Nerves A Guide to the Cranial Nerves A Guide to the Cranial Nerves  Spinal Cord Location: attached to the brain stem 31 pairs (with Coccygeal nerve) Conduit of information (brain–body) Skin, joints, muscles Spinal nerves Dorsal root Ventral root Spinal Cord Spinal Cord CNS: Important Structures CNS: Amygdala and Substantia Nigra CNS: LGN, MGN, & the Hippocampus CNS: Medullary Pyramid & Cochlear nuclei The Blood Supply of the Brain The Blood Supply of the Brain The Blood Supply of the Brain IMAGING THE BRAIN  New Views of the Brain Historically, dissection and staining Difficult to visualize and reconstruct deep structures in three dimensions New CLARITY method – clarified brain, transparent. Light-absorbing lipids are replaced with water-soluble gel. GFP – green fluorescent protein molecules can reveal deep regions.  The Challenges of the Connectome Connectome of the neocortex: a detailed wiring diagram of connections The challenge of 100 million synapses in the human neocortical cylinder Brenner’s work on flatworm’s 7000 synapses – over a dozen years Seung’s new work with computational technologies for analyzing neural circuits  X-rays and Computed Tomography (CT) Radiopaque material X-rays are two dimensional Great for bone structures CT - Hounsfields and Cormack (1979 Nobel Prize) Generates an image of a brain slice (tomography = cut/section) X-ray beams used to generate data for a digitally reconstructed image Living brains in 3D Contrast agents (blood vessels) https://www.fda.gov/radiation-emitting-products/medical-x- ray-imaging/what-computed-tomography  Magnetic Resonance Imaging (MRI) Based on how hydrogen atoms respond in the brain to perturbations of a strong magnetic field Hydrogen atoms resonate proton between high and low energy states Signals mapped by computer to create imagery Advantages of MRI over CT More detail Does not require X-irradiation Brain slice image in any angle ~15 minutes to compute the imagery  Diffusion Tensor Imaging MRI (water diffuses faster along the fatty axons rather than across. Brain connectivity revealed  Imaging Brain Activity 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.  Imaging Brain Activity - PET Positron emission tomography (PET) Radioactively labeled 2- Deoxyglucose (2-DG) Active neurons consume 2-DG Limitations: Radioactivity Spatial resolution of 5-10mm3 Basic principles Active neurons demand more glucose, thus more blood to active regions. Indirect neuronal activity  Imaging Brain Activity - fMRI Functional MRI (fMRI) Ratio of Oxyhemoglobin vs Deoxyhemoglobin Resolution of 3mm3 Single image can be obtained in seconds Non-invasive, non-irradiating Imaging technique of choice Need for greater spatiotemporal resolution and better patient experience Autism spectrum disorder, functional MRI and MR spectroscopy: possibilities and challenges (2012) Kenneth Hugdahl, Mona K Beyer, Maiken Brix, Lars Ersland  Putting Images Together – Clinical Case DBS – deep brain stimulation (Parkinson’s disease)  CHEMICAL SENSES Animals depend on the chemical senses to identify nourishment, poison, or potential mate. Chemical sensation Oldest and most common sensory system Nourishment Noxious stimuli detection Finding a Mate Chemical senses Gustation Olfaction Chemoreceptors Wide distribution  The Basic Tastes Saltiness, sourness, sweetness, bitterness, and umami Possibly fat, starch, carbonation, calcium, water Examples of correspondence between chemistry and taste Sweet—sugars like fructose, sucrose, artificial sweeteners (saccharin and aspartame) Bitter—ions like K+ and Mg2+, quinine, and caffeine Advantage for survival Poisonous substances—often bitter  Flavour of the Day Distinguishing the countless unique flavours of food Each food activates a different combination of taste receptors. Distinctive smell Other sensory modalities contribute.  The Organs of Taste Areas of sensitivity Tip of the tongue - Sweetness Back of the tongue - Bitterness Sides of tongues - Saltiness & sourness Foliate papillae Vallate papillae Fungiform papillae Threshold concentration Just enough exposure of single papilla to detect taste 2,000-5,000 Taste Buds 1TB - ~50-150 Taste Cells (regenerate every 2 weeks) Taste Responsiveness of Taste Cells  Mechanisms of Taste Transduction Taste stimuli (tastants) may: Pass directly through ion channels (salt and sour) Bind to and block ion channels (sour) Bind to G-protein-coupled receptors and activate second messenger to open ion channels (bitter, sweet, umami)  Saltiness Sourness Bitterness Sweetness Umami Salt-sensitive cells High acidity—low pH Families of taste receptor genes – T1R Special Na+-selective and T2R channel  Taste Receptors Bitter – T2Rs Sweet – T1R2+T1R3 Umami – T1R1+T1R3  Central Taste Pathways Cranial nerves—gustatory nucleus—primary gustatory cortex Localized lesions Ageusia: the loss of taste perception Gustation Important to the control of feeding and digestion Hypothalamus Basal telencephalon  The Neural Coding of Taste Labeled line hypothesis Individual taste receptor cells for each stimuli In reality, most neurons are broadly tuned. Population coding Roughly labeled lines Large numbers of broadly tuned neurons Contribution of temperature and textural features of food  Smell Warns of harmful substances, combines with taste for identifying foods Pheromones—a mode of communication: Reproductive behaviour Territorial boundaries Identification of individuals Signal aggression or submission Role of human pheromones unclear Vomeronasal organ  The Organs of Smell Odorants: activate transduction processes in neurons Anosmia: inability to smell Humans: weak smellers compared to many animals due to small surface area of olfactory epithelium Transduction Mechanisms of Vertebrate Olfactory Receptor Cells Olfactory Receptor Cell during Stimulation  Maps of Expression of Olfactory Receptor Proteins Rodents - 1000 genes Humans - 350 genes Broad Tuning of Single Olfactory Receptor Cells Location and Mapping of an Olfactory Bulb  Central Olfactory Pathways Axons of the olfactory tract: branch and enter the forebrain Neocortex: reached by a pathway that synapses in the medial dorsal nucleus of thalamus Spatial and Temporal Representations of Olfactory Information Olfactory population coding Olfactory maps (sensory [activity] maps) Temporal Coding in the Olfactory System Temporal patterns of spiking in olfactory neurons Oscillations of activity when odors are presented to the receptors— relevance unknown Temporal patterns also evident in spatial odor maps City and Campus (??) Odour [Sensory] Maps  Concluding Remarks Variety of transduction mechanisms in gustation and olfaction Molecular mechanisms similar to signaling systems used in every cell of the body Common sensory principles Broadly tuned cells Population coding Sensory maps in brain Timing of action potentials may represent sensory information in ways not yet understood.  THE EYE The Visual System The Eye/Retina - Photoreceptors: convert light energy into neural activity - Detects differences in intensity of light - Comparison of human eye and camera Lateral geniculate nucleus (LGN) Visual Cortex (V1…)  Properties of Light Light Electromagnetic radiation Wavelength, frequency, amplitude Energy is proportional to frequency.  Properties of Light and Interactions Optics Study of light rays and their interactions Reflection Bouncing of light rays off a surface Absorption Transfer of light energy to a particle or surface Refraction Bending of light rays from one medium to another  Gross Anatomy of the Eye Pupil: opening where light enters the eye Sclera: white of the eye Iris: gives color to eyes Cornea: glassy transparent external surface of the eye Optic nerve: bundle of axons from the retina Cross-Sectional Anatomy of the Eye  Accommodation by the Lens Eye collects light, focuses on retina, and forms image. Changing shape of lens provides extra focusing power. Emmetropia, Myopia, and Hyperopia  The Visual Field Amount of space viewed by retina when eye is fixated straight ahead Visual acuity: ability to distinguish two nearby points Visual angle: distance across the retina described in degrees  Microscopic Anatomy of the Retina Photoreceptors to Bipolar cells to Ganglion cells Retinal processing also influenced by lateral connections Horizontal cells Receive input from photoreceptors and project to other photoreceptors and bipolar cells Amacrine cells Receive input from bipolar cells and project to ganglion cells, bipolar cells, and other amacrine cells Laminar Organization of the Retina  Photoreceptor Structure Converts electromagnetic radiation to neural signals Four main regions Outer segment Inner segment Cell body Synaptic terminal Types of photoreceptors Rods and cones Rods: long, cylindrical outer segment with many disks Cones: shorter, tapering outer segment with fewer disks Rods over 1000 times more sensitive to light than cones Differences in rods and cones: “duplex retina”  Regional Differences in Retinal Structure Structure varies from fovea to retinal periphery. Peripheral retina Higher ratio of rods to cones Higher ratio of photoreceptors to ganglion cells More sensitive to low light Cross section of fovea: pit in retina where outer layers are pushed aside Maximizes visual acuity Central fovea: all cones (no rods) Area of highest visual acuity  Phototransduction Phototransduction in rods Light energy interacts with photopigment. Produces a change in membrane potential G-protein-coupled receptor causes a change in second messenger  Phototransduction in Rods Dark current: Rod outer segments are depolarized in the dark because of steady influx of Na+. Photoreceptors hyperpolarize in response to light.  Phototransduction in Rods Light-activated biochemical cascade in a photoreceptor The consequence of this biochemical cascade is signal amplification—sensitivity to small amounts of light.  Ganglion Cell Photoreceptors Intrinsically photosensitive retinal ganglion cells  Phototransduction in Cones Similar process to rod phototransduction Different opsins Red (long wavelength), green (medium wavelength), blue (short wavelength) Color perception Contributions of blue, green, and red cones to retinal signal Young—Helmholtz trichromacy theory of color vision  Mixing Colors Mixing of red, green, and blue light causes equal activation of the three types of cones. The perception of “white” results  The Receptive Field Area of retina where light changes neuron’s firing rate Fields change in shape and stimulus specificity. Receptive field: ON and OFF bipolar cells Receptive field: Stimulation in a small part of the visual field changes a cell’s membrane potential. Antagonistic center-surround receptive fields  Concluding Remarks Light emitted by or reflected off objects in space is imaged onto the retina. Transduction Light energy converted into membrane potential changes Phototransduction parallels olfactory transduction Electrical-to-chemical-electrical signal Mapping of visual space onto retina cells not uniform (97 million photoreceptors and 1 million RGCs) THE CENTRAL VISUAL SYSTEM Retinal Receptive Fields The Visual Pathway that Mediates Conscious Visual Perception Visual Field Deficits from Lesions in the Retinofugal Projection  Nonthalamic Targets of the Optic Tract Hypothalamus: role in biological rhythms, including sleep and wakefulness Pretectum: control size of the pupil, certain types of eye movement Superior colliculus: orients the eyes in response to new stimuli—move fovea to objects of interest Retinal Inputs to the LGN layers  Organization of the LGN Inputs segregated by eye and ganglion cell type Primary visual cortex provides 80% of the synaptic input to the LGN—role not clearly identified. “Top–down” modulation may gate “bottom-up” input from LGN back to cortex. Brain stem neurons provide modulatory influence on neuronal activity.  Receptive Fields Receptive fields of LGN neurons: almost identical to the ganglion cells that feed them Magnocellular LGN neurons: large center-surround receptive fields with transient response Parvocellular LGN cells: small center-surround receptive fields with sustained response Anatomy of the Striate Cortex  The Retinotopic Map in the Striate Cortex Map of the visual field onto a target structure (retina, LGN, superior colliculus, striate cortex) Central visual field (fovea) overrepresented in map Discrete point of light can activate many cells in the target structure due to overlapping receptive fields.  Architecture of the Striate Cortex Layers I to VI Spiny stellate cells: spine-covered dendrites—layer IVC Pyramidal cells: spines and thick apical dendrite—layers III, IVB, V, VI Inhibitory neurons: lack spines—all cortical layers—form local connections  Inputs to the Striate Cortex Magnocellular LGN neurons project primarily to layer IVC. Parvocellular LGN neurons project to layer IVC. Koniocellular LGN axons make synapses primarily in layers I and III.  Patterns of Intracortical Connections & Outputs Radial vs Horizontal Connections Layer II, III, and IVB cells project to other cortical areas. Layer V cells project to the superior colliculus and pons. Layer VI cells project back to the LGN.  Ocular Dominance Columns Studied with transneuronal autoradiography from retina, to LGN, to striate cortex Present in layer IV of macaque monkey striate cortex— showing alternating inputs from two eyes  Mixing of Information from the Two Eyes First binocular neurons found in striate cortex—most layer III neurons are binocular (but not layer IV). Ocular Dominance and Developmental Plasticity  Cytochrome Oxidase Blobs Cytochrome oxidase: mitochondrial enzyme used for cell metabolism Blobs: cytochrome oxidase- stained pillars in striate cortex Each blob centered on an ocular dominance column in layer IV. Receive koniocellular inputs from LGN  Physiology of the Striate Cortex Monocular receptive fields Layer IVC: similar to LGN cells Layer IVC: insensitive to the wavelength Layer IVC: center-surround color opponency Binocular receptive fields Most neurons in layers superficial to IVC are binocular. Two receptive fields—one for each eye Orientation Selectivity  Direction Selectivity Neuron fires action potentials in direction-dependent response to moving bar of light.  A Simple Cell Receptive Field Simple cells: binocular, orientation-selective, elongated ON or OFF area flanked with antagonistic surround Receptive field may be composed of three LGN inputs from cells with aligned center-surround receptive fields. PRIMAL SKETCH in V1  Parallel Pathways Magnocellular, blob, and parvo-interblob pathways  Complex Cell Receptive Field Complex cells: binocular, orientation-selective, ON and OFF responses to the bar of light but unlike simple cells, no distinct ON and OFF regions Cortical Module Intrinsic Optical Imaging and Calcium Imaging  Cortical Module Each module capable of analyzing every aspect of a portion of the visual field Cortical Module Visual Areas in Human Brain  Beyond the Striate Cortex Dorsal stream Analysis of visual motion and the visual control of action V1, V2, V3, MT, MST, other dorsal areas Area MT (temporal lobe) direction-selective, respond more to the motion of objects than their shape. MST (parietal lobe) Navigation Directing eye movements Motion perception Ventral stream Perception of the visual world & recognition of objects V1, V2, V3, V4, IT, other ventral areas Area V4—shape and color perception Achromatopsia: clinical syndrome caused by damage to area V4—partial or complete loss of color vision Area IT Major output of V4 Receptive fields respond to a wide variety of colors and abstract shapes. May be important for both visual perception and visual memory (such as faces) Parallel Processing and Perception Visual perception Identifying and assigning meaning to objects Hierarchy of complex receptive fields In retinal ganglion cells: center-surround structure, sensitive to contrast and wavelength of light Loading… In striate cortex: orientation selectivity, direction selectivity, and binocularity Extrastriate cortical areas: selective responsive to complex shapes (faces) and motion Parallel processing and perception Groups of cortical areas contribute to the perception of color, motion, and object meaning.  Concluding Remarks Vision Perception combines individually identified properties of visual objects: color, form, movement Achieved by simultaneous, parallel processing in several visual pathways Parallel processing More like the sound produced by an orchestra than by individual musicians