Neuro Kapitel 1.docx

[Lecture ] Function of nervous systems, types of nerve cells, structure of nerve cells, excitable & non-excitable parts of nerve cells, signal transduction in axons, glial cells, myelin, electric properties of cellular membranes, ion channels, patch clamp, voltage sensors [Information transfer in...

[Lecture ] Function of nervous systems, types of nerve cells, structure of nerve cells, excitable & non-excitable parts of nerve cells, signal transduction in axons, glial cells, myelin, electric properties of cellular membranes, ion channels, patch clamp, voltage sensors [Information transfer in organisms through:] - Hormones as chemical messengers (slower) transfer speed: 0.1 m/s but long effects (duration of effect: s -- days) - Nerve Signal as electrical information transfer (faster) communication along the cell membrane signal speed: 1-120 m/s but shorter effects (duration of effect: ms -- min) - **fast transfer** of information leading to **physiological effects of short duration** are general achieved through nerve **signals** - **slower transfer** of information leading to **longer lasting physiological effects** are in general achieved through **hormones** - **simplest form of a nervous system is a neural net multipolar nerve cells are distributed between ecto- & endodermal cells (is not clearly distinguishable from the rest of the body)** - **ectoderm: outermost layer that forms nails, hair, etc.** - **endoderm: innermost layer that forms stomach, colon, urinary bladder, etc.** - **cells spread in all directions with decreasing strength via single pulses** - **neural nets are also found in cnidaria & in the enteric nervous system of vertebrates** - **more dense concentration of neurons around sensory organs in evolutionary more developed organisms neurons are concentrated either in ganglia or nerve cords specialization and fusion of body segments can lead to development of brains in limbed animals** - **faster or more complex cascades in these parts** - **usually around fins/arms/primitive organs** - **ganglia = "mini brains" along the body (often in insects) bundle of nerves** - **radial symmetry animals vs. bilateral symmetry animals** - **radial symmetry:** - **multiple symmetry axis along the body** - **body parts extend outward from the center of the body in an equal distribution** - **e.g. starfish** - **is the oldest form of organisms** - **bilateral symmetry:** - **one symmetry axis divides the animal into two equal parts** - **"newer" form as these evolved, the neural networks also evolved & becoming more complex with more structural systems** - **sub-structured bodies with more complex neuronal structures** - evolution of neuronal networks/systems - evolution is a conservative process - once a structure is developed, it is used consecutively - evolution from neuronal network to formation of ganglia to specific brains to structured, more complex neuronal systems in a sub-structured body with multiple limbs & protrusion - first neuronal networks were simple networks in primitive animals - primitive networks = primitive behavior - with growing numbers of neurons, the complexity of network and behavior increases systems form - **processing of new sensory information & activation of effector systems can be visualized** - **NMR/MRT: functional magnetic resonance imaging** - **PET: positron-emission-tomography** - **but overall really difficult to pinpoint regions of the brain to only certain action** - **there are spatial segregations but they look the same no structural differences** **[nervous system and behavior]** - larger number of neurons in a nervous system and higher degrees of networking among neurons allow larger capacities to take up, process and use information **sum of all activities on whole animal level = behavior** - number of neurons correlate in some way with cognitive capacity but not always with the size of the animals - capacity to learn - many complex behaviors (self-awareness) is learned & it's not something we're born with - more simple nervous networks allow stereotypical reactions to specific trigger - very little modulation its always the same - BUT simple learning/habituation is possible - habituation: decrease in response to a stimulus as a result of repeated presentation of the stimulus - complex nervous networks allow complex learning and certain freedom of choice and awareness - more complex = nervous system; more simple = nervous network - size of the brain is not as important more important is density of neurons [anatomy of a neuron] - difference between neurons and any other cell: neurons stop reproducing at some point - neuronal networks could not be build any other way because formed connections would be lost when neurons would continue to reproduce - if a connection is formed, it is relatively stable for a certain amount of time - structure: - soma with nucleus perikaryon - dendrites - axon - synapse - accessory cells of the nervous system (glia) - oligodendrocytes (CNS) - Schwann-cells (peripheral nervous system) - [different types of neurons] - invertebrate neuron - cell body with axon & dendrites - pseudounipolar cell - cell body with central axon & peripheral axon to skin & muscle - bipolar - axon with cell body & dendrites - characteristic of axon not always clear = neurite is the more appropriate term - neurite = any projection from the cell body of a neuron (axon/dendrite) - "lazy term" - not always simple to differentiate axon from dendrite/specific role of projection - is it a receiving/output part of the cell? (needs to be experimentally determined) Ein Bild, das Text, Diagramm, Skelett enthält. Automatisch generierte Beschreibung - [special types of neurons in vertebrates] - spinal motor neuron - pyramid cells in the hippocampus - Purkinje-cells of cerebellum  - even though the anatomy is very different in different neurons, the overall functional anatomy is similar same sequence of events Ein Bild, das Text, Entwurf, Zeichnung, Diagramm enthält. Automatisch generierte Beschreibung [comparison of the invertebrate & vertebrate CNS] - ganglia vs. spinal cord - process of processing is quite similar on this level - neurons coming in, forming synapses, information is transmitted locally & then travels to a different part - ganglia = nerve cell cluster - each ganglion is responsible for one part of the body  - level of comparison breaks away on higher processing levels - vertebrates have brains as their main processing part - from ganglia-based to stratified/layered structure - main processing region in invertebrates stays ganglia-based - with evolution, the head-ganglia grew in size more power to the head/brain [Glial cells in vertebrates ] - neurons do not operate alone but are part of a neuronal system with all different kind of cells - other neuronal cells that do not participate in the direct transportation of signals - participate indirectly by providing support/nutrients or removing waste - Glia cells are the "glue of the nervous system" - overall more glia cells then neurons - glia cells are not neurons because they cannot transmit information - provide physical/structural **and** chemical support to neurons and maintain their environment - different types of glial cells in CNS with specific roles - **Astrocytes** - most common type of glial cells - protoplasmic astrocytes (thick with lots of branches; in the gray matter of the brain) & fibrous astrocytes (longer & slender with few branches, in the white matter of the brain) have similar jobs - forming the **blood-brain barrier** (filtering system) - contains fatty material so that non-fat-soluble substances (as many harmful substances are) have difficulty passing through it - reason why brain relies strongly on glucose - glucose transporter can pass through blood-brain barrier (unlike other substances that could provide energy) - AND glucose gives high yield and degradation for energy production is very fast - regulating neurotransmitters (recycling) - cleaning up (after a neuron dies; excess potassium ions) - regulating blood flow to the brain - synchronizing the activity of axons - brain energy metabolism and homeostasis - **Oligodendrocytes** - main purpose: help information move faster **electrical insulation** - wrap around axons & form protective layer myelin sheath - gap between = node of Ranvier; node that helps spread the electrical signal (signal hops from one node to the next) - **Microglia** - tiny glial cells - brain's own dedicated **immune system** - alert to signs of injury and disease clearing away dead cells or getting rid of toxins/pathogens - housekeeping role in learning-associated bran plasticity & guiding the development of the brain - Ependymal cells - make up thin membrane lining of the central canal of the spinal cord and the ventricles of the brain - have little hairlike projections called cilia that wave back and forth to keep cerebrospinal fluid circulating - fluid delivers nutrient and eliminates waste products form the brain & spinal column - necessary to maintain homeostasis (e.g. regulating its temperature) - also functions as a cushion/shock-absorber between brain and skull - Radial glia - type of stem cell that can create other cells - contribute to the brains ability to change & adapt neuroplasticity - different types of glial cells in peripheral nervous system (PNS) - **Schwann cells** - function like oligodendrocytes **provide myelin sheaths for axons in PNS** - but one Schwann cells surrounds one axon (oligodendrocytes can spread out & myelinate a few cells) - also **part of immune systems of the PNS** - when nerve cell is damaged they can "eat"/destroy the nerve's axon and provide path for a new axon to form - can be involved in some form of chronic pain - Satellite cells - surround certain neurons with a sheath around the cellular surface - believed to be similar to astrocytes - main purpose: regulating the environment around neuron keeping chemicals in balance - neurons with satellite cells make up clusters of nerve cells called ganglia - in autonomic nervous system (NS for internal organs) & in sensory system (NS for senses) - can deliver nutrients to neurons and can absorb toxins like metals [Electric properties of the neuron plasma membrane (PM)] - PM posses lipid bilayer that is impermeable to charged particles is electric insulator - but active transporters (e.g. Na^+^/K^+^-ATPase) or passive carriers/channels (Sodium (N) or Potassium (K) channels) allow ions to pass through the membrane - potential difference is force/power and can be used - electrical properties are primarily regulated through Na^+^ & K^+^ - **influenced by** - **concentration difference between intra- & extracellular space** - **permeability of the PM** - Na^+^/K^+^-ATPase maintains concentration gradient across membrane - electrogenic pump = 3 Na^+^ out & 2 K^+^ in per cycle - creates net differences transports net charges Ein Bild, das Text, Schrift, Screenshot, weiß enthält. Automatisch generierte Beschreibung electrogenic pump! - because of their unequal distribution/gradient, whenever channel opens, a small amount of these ion pass through the membrane - bc of the huge concentration differences, they are very motivated to move along their gradient - changing the permeability of the PM to charged ions important so cell can make sure that only specific ions are able to pass through and other can't unspecific channels would not allow us to use the force that is build up (potential would be neutralized) - specificity is very important for potential building & usage - ions are "judged" by channel properties by charge type, size and diameter of the ion (if the ion is hydrated or dehydrated) - channels usually let specific ions through (but unspecific cation channels exist) - selectivity filters of ion channels - external selectivity filter - e.g. cation channels can have negative charges on the outside so negatively charged molecules/ions are electrostatically repelled - internal selectivity filter - have specific binding sides inside the channel which only stabilizes passage of a specific ion - passage also possible by hybridization of the ion (binding of water) [the patch clamp method] - electrophysiological technique that can directly measure the membrane potential &/or amount of current passing across cell membrane - allows insight into function of ion channels and membrane properties at single-cell-level - process - sealing a glass pipette to the cell membrane under a microscope - tip of the pipette is brought into contact with cell membrane and by applying suction/negative pressure, a small patch of membrane is pulled into the tip of the pipette and a tight seal is formed - high-resistant seal or whole-cell configuration - two primary configuration of the method - "cell-attached": seal between pipette and membrane has high resistance, allowing recording of ion channel activity directly at the membrane - "whole-cell": additional suction to rupture the membrane and to establish electrical contact between pipette and cytoplasm; allows extensive manipulation of the cell's internal environment - recording ion currents - small voltage across the membrane/cell interior through amplifier - by measuring the resulting ionic currents flowing through ion channels, conductance, kinetics & selectivity can be characterized of these channels - amplifier also allows control of voltage across the membrane study of voltage-gated ion channels possible - membrane potential (Vm) = voltage difference over a biological membrane = difference between potential inside the cell compared to outside the cell - measurement through "voltage clamp" electrode inside the cell - **membrane potential is always inside vs. outside** [Ion Channels] - conductivity of ion channels - equilibrating channels (Gleichgewicht) - allow ion flow across membrane in both directions equilibrium potential with no net movement of ions - typically no significant selectivity permit ions to flow down their electrochemical gradient until equilibrium is reached - rectifying channels - asymmetry in their ion conductance properties only/preferentially allow ion flow just in one direction over the other - more permeable in one direction than the reverse direction rectification of the ion current - play a part in controlling resting membrane potential and the shaping of action potentials - electrical signal is unidirectional - Gramicidines are peptides form *Bacillus brevis* antibiotic effects, pore-building toxin - "artificial" ion channel opens & closes in a voltage dependent manner - creates a perfect equilibrating channel - is ionophore = molecule that allows transport through membrane - current flow through an ion channel is a saturation function - flow increases with increasing ion concentration but ion channel lumen can only hold a certain number ions per time unit I~max~ (maximal single channel current) is reaches, when the channel is fully saturated with ions operate just like enzymes Ein Bild, das Diagramm, Reihe, Text enthält. Automatisch generierte Beschreibung [Regulation of ion channel function] - flow of current through an open ion channel is constant until channel closes or is inactivated driven through conformational changes of the channel protein - open/close physical prevention of flow - active/inactive channel is open but is not leading current - mechanisms (gating) - Ligand activated ion channels (A) - ion channels can be opened/closed by binding of extracellular messenger molecules that bind to receptor domain on the channel - different modulation possible - endogenous agonist - opens the channel "normally" - reversible agonist - blocks the binding site and keeps the channel closed - is reversible - irreversible antagonist - blocks the binding site and keeps the channel closed irreversibly - exogenous agonist - binds at a different binding site and can also open the channel - opening of an ion channel through protein phosphorylation (B) - channel protein has Aas in cytosolic domain and phosphorylation of that domain leads to ΔKonf. which opens the ion channel - can be many other PTM - voltage gated ion channels (C) - channels can be open through depolarization of the membrane potential above a critical threshold - voltage sensor is part of the channel's protein structure - "sliding helix" hypothesis - depolarizing the membrane above a threshold twists certain domain of helix structure (S4-transmembrane domain) from its metastable conformation - positively charged Arg-side groups stabilize the channel in open position through interaction with negative charge at the next level - different closing mechanisms - intrinsic inactivation (refractivity) - inactivation through the transported ion (binds to certain side on cytoplasmic side of channel) - inactivation through protein phosphorylation of the channel protein - stretch-activated ion channels (D) - channel proteins can be connected to cortical actin system which is part of the cytoskeleton - ΔKonf. when plasma membrane is stretched due to internal/external pressure - present in many mechano-sensors  [building an ion channel] - ion channels can be hetero-multimeric, homo-multimeric or can consist of pseudo-subunits - topology of an ion cannel subunit - certain transmembrane regions but also regions that reach into cytoplasm or extracellular room - hydrophobicity plots can provide insights into position of transmembrane regions and extra-/intracellular domains - shows how hydrophobic/hydrophilic certain regions are - amino acid sequence of subunits of Na^+^/Ca^+^/K^+^ channels overlap between 27-50% among animals probably homologs Ein Bild, das Text, Diagramm, Handschrift, Reihe enthält. Automatisch generierte Beschreibung [inactivation & refractivity ] - intrinsic inactivation (A) - inactivation through the transported ion (B) - inactions through protein phosphorylation of the channel protein (C) - more complex