Download Document

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Endocannabinoid system wikipedia , lookup

Apical dendrite wikipedia , lookup

Resting potential wikipedia , lookup

Signal transduction wikipedia , lookup

Premovement neuronal activity wikipedia , lookup

Membrane potential wikipedia , lookup

Neuromuscular junction wikipedia , lookup

Subventricular zone wikipedia , lookup

Multielectrode array wikipedia , lookup

Rheobase wikipedia , lookup

Action potential wikipedia , lookup

Clinical neurochemistry wikipedia , lookup

Single-unit recording wikipedia , lookup

Biological neuron model wikipedia , lookup

Nonsynaptic plasticity wikipedia , lookup

Neuroregeneration wikipedia , lookup

Axon guidance wikipedia , lookup

Pre-Bötzinger complex wikipedia , lookup

Optogenetics wikipedia , lookup

End-plate potential wikipedia , lookup

Electrophysiology wikipedia , lookup

Circumventricular organs wikipedia , lookup

Development of the nervous system wikipedia , lookup

Neurotransmitter wikipedia , lookup

Feature detection (nervous system) wikipedia , lookup

Synaptic gating wikipedia , lookup

Nervous system network models wikipedia , lookup

Synaptogenesis wikipedia , lookup

Neuroanatomy wikipedia , lookup

Axon wikipedia , lookup

Chemical synapse wikipedia , lookup

Node of Ranvier wikipedia , lookup

Molecular neuroscience wikipedia , lookup

Stimulus (physiology) wikipedia , lookup

Neuropsychopharmacology wikipedia , lookup

Channelrhodopsin wikipedia , lookup

Transcript
MOLECULAR
AND
CELLULAR
NEUROSCIENCE
BMP-218
November 4, 2014
Tuesday, November 4, 14
DIVISIONS OF THE NERVOUS SYSTEM
The nervous system is composed of two primary divisions:
Tuesday, November 4, 14
1. CNS - Central Nervous System (Brain + Spinal Cord)
2. PNS - Peripheral Nervous System (Nerves + Ganglia)
CELLS OF THE NERVOUS SYSTEM
The nervous system is composed of two primary types of cells:
Tuesday, November 4, 14
1. Neurons
- transmit information
2. Glia
- largely supporting cells
NEURONS
Occur in a wide variety of sizes and shapes, but all share the feature of “cell-to-cell” communication
Tuesday, November 4, 14
NEURONAL CYTOARCHITECTURE
Dendrites
•
Receives signals from other cells (Input)
Cell Body (Soma/Perikaryon)
•
Contains cell nucleus
Initial Segment/Axon Hillock
•
Integrates information
•
Fires an “action potential” (explained later)
Axon
•
Projects to other cells for communication
•
Other neurons, muscles, organs
Axon Terminal / Synapses
•
Release of neurotransmitters
Tuesday, November 4, 14
MYELIN
• Multilayered lipid and protein covering axons at certain areas
• Electrically insulates axons and increases speed of conduction
-
Nodes of Ranvier separate myelinated areas and are important in saltatory conduction
• Produced by Oligodendrocytes in the CNS and Schwann Cells in the PNS
-
Oligodendrocytes myelinate multiple axons
-
Schwann cells myelinate a single axon
Schwann Cell
Tuesday, November 4, 14
Oligodendrocyte
MYELIN
Tuesday, November 4, 14
•
Myelin sheath is formed from multiple tight layers
•
This restricted molecular mobility gives rise to unique characteristics on MRI
GRAY AND WHITE MATTER
Gray Matter
•
Contains neurons, dendrites, axons without myelin, soma
•
Does not contain myelin
•
Cerebral cortex (surface of the brain)
•
Deep parts of the brain (nuclei) containing neuron cell bodies
•
Central regions of the spinal cord
White Matter
Tuesday, November 4, 14
•
Contains myelin
•
Parallel axons surrounded by myelin that traverse from one part of the nervous system to another
•
Peripheral regions of the spinal cord
MYELIN STAINED TISSUE SECTION OF HUMAN BRAIN
White Matter
(Stained Dark)
Gray Matter
(No Stain)
Tuesday, November 4, 14
TYPES OF NEURONS
Tuesday, November 4, 14
CLASSIFICATIONS OF NEURONS
Afferent Neurons
• Transmits information into the CNS from receptors
• Cell body and long peripheral process of the axon are in the PNS; only the short central process enters the CNS
• Have no dendrites (do not receive inputs from other neurons)
Efferent Neurons
• Transmit information out of CNS to effector cells (muscles, glands, other neurons)
• Cell body, dendrites, and a small segment of the axon are in the CNS; most of the axon is in the PNS
Interneurons
• Function as integrators and signal changers
• Integrate groups of afferent and efferent neurons into reflex circuits
• Entirely in the CNS; 99% of all neurons
Tuesday, November 4, 14
GLIA
Subtypes include:
•
Astrocytes
•
Oligodendrocytes
•
Microglia
•
Ependymal Cells
•
Choroidal Cells
Glia Provide
Tuesday, November 4, 14
•
Physical (structural) support for surrounding neurons
•
Metabolic support for surrounding neurons
•
Immune function
•
Myelin (Oligodendrocytes in CNS; Schwann Cells in PNS)
•
Communication? (Calcium channel communication between astrocytes)
ASTROCYTES
• In development, guide neurons as they migrate to their destinations
• Stimulate neuronal growth by secreting growth factors
• Forms the Blood-Brain Barrier (BBB), connecting neurons to blood vessels
Tuesday, November 4, 14
ASTROCYTES
• In development, guide neurons as they migrate to their destinations
• Stimulate neuronal growth by secreting growth factors
• Forms the Blood-Brain Barrier (BBB), connecting neurons to blood vessels
• Most common type of primary brain tumor (astrocytoma)
Hayden EC, Nature. 2010; 463(7278):154-6.
Tuesday, November 4, 14
OLIGODENDROCYTES
Forms the myelin covering of CNS
Tuesday, November 4, 14
MICROGLIA
• The main phagocytic cell and antigen-presenting cells in the CNS
• Smallest cell bodies among the neuroglia
• Immune response / injury
Tuesday, November 4, 14
EPENDYMAL AND CHOROIDAL CELLS
• Considered “glial like” cells
• Ependymal Cells
•
Line the ventricular system in CNS
•
Regulate the production and flow of cerebrospinal fluid (CSF)
• Choroidal Cells
Tuesday, November 4, 14
•
Form the inner layer of the choroid plexus which abuts the ventricular system in specific locations
•
Secretes CSF into the ventricles
NEUROPHYSIOLOGY
Tuesday, November 4, 14
NEUROPHYSIOLOGY
Signaling within groups of neurons depends on three (3) basic properties of these cells:
1. The resting membrane potential (most cells)
• Negative charge on the inside of the cell
• Positive charge on the outside of the cell
• RMP ranges from -30mV to -90mV (typically -70mV)
• [Na+] high on the outside and [K+] high on the inside
2. Transmembrane protein ion channels (in neurons)
• Transmission of signal along surface of the cell
• Controlled (gated permeability) to both K+ and Na+
3. Projections to other neurons and synapses
• Between cell signal propagation via a chemical intermediate
Tuesday, November 4, 14
ION CHANNELS
(Gated) Ion Channels
Na +/K + ATPase
Na+/K+ ATPase
Uses energy stored in ATP (which is formed mostly by mitochondrial oxidative glucose metabolism) to maintain
transmembrane gradients of K+ and Na+
Transports 3 Na+ out while bringing in 2 K+
Tuesday, November 4, 14
ION CHANNELS
(Gated) Ion Channels
Na +/K + ATPase
Gated Ion Channels
Allow Na+ and K+ to flow down their concentration gradients
Formation of transmembrane electric current
(Partial) collapse of RMP when gates are open
Gates are controlled by transmembrane voltage (transistor-like properties)
Tuesday, November 4, 14
THE ACTION POTENTIAL
Tuesday, November 4, 14
ACTION POTENTIAL
• The action potential is a wave of transient depolarization that travels along the neuron and particularly the axon
• Depolarization causes voltage sensitive ion channels to open to propagate depolarization
– Na+ flows inward (sodium current)
– K+ flows outward (potassium current)
• Myelin and Nodes of Ranvier speed the conduction
• Pharmacology of voltage sensitive channels
– Site of action of neurotoxic drugs (snake venom, scorpion toxins, plant alkaloids etc)
– Site of action of local anesthetics (lidocaine)
Tuesday, November 4, 14
ACTION POTENTIAL
repolarization
depolarization
Hodgkin-Huxley model
• Developed in 1950’s through voltage
recordings with intracellular and
extracellular electrodes in squid giant
axons
hyperpolarization
Depolarization: Na+ and K+ channels open
Repolarization: Na+ channels close and K+ open
Hyperpolarization: K+ channels still open
Tuesday, November 4, 14
CONDUCTION
A
B
A. Conduction in an unmyelinated fiber.
• Na+ flows in depolarizing adjacent sections of membrane.
• Self propagating
B. Saltatory conduction in myelinated fibers.
• Myelin insulates and blocks current across membrane
• Depolarization occurs at Nodes of Ranvier
• Current “jumps” from node to node
• Faster and more energy efficient
Tuesday, November 4, 14
INTERCELLULAR COMMUNICATION
Presynaptic neuron
Postsynaptic neuron
Tuesday, November 4, 14
SYNAPTIC FUNCTION & NEUROTRANSMISSION
Signal conveyed by neurotransmitter diffusion across synaptic cleft
•
Presynaptic electrical signal converted to a chemical signal that is reconverted to an electrical signal in the postsynaptic
cell
•
Slow compared to action potential propagation
Specific networks of nerve cells tend to use specific neurotransmitters
•
•
•
Anatomically based networks use specific neurotransmitters
Inhibitory neurons frequently use dopamine and GABA
Excitatory neurons frequently use glutamate and acetylcholine
Tuesday, November 4, 14
SYNAPTIC TRANSMISSION
Presynaptic events
•depolarization opens Na+ and Ca2 + channels.
•influx of Ca2 + causes docking and
exocytotsis of neurotransmitter (NT)
•vesicles into the synaptic cleft
Postsynaptic events
•NT binds to receptors and opens ion
channels that depolarize the membrane
(excitatory postsynaptic potential (EPSP)) or
hyperpolarize the postsynaptic membrane
(inhibitory postsynaptic membrane (IPSP).
Glial cells remove neurotransmitter from the synaptic cleft
Tuesday, November 4, 14
A single impulse doesn’t initiate an action potential in the post-synaptic neuron
• partially depolarize neuron and bring it closer to threshold or
• hyperpolarize the postsynaptic neuron and make it harder to depolarize
Tuesday, November 4, 14
NEUROTRANSMITTERS
Tuesday, November 4, 14
NEUROTRANSMITTER RECEPTORS
Tuesday, November 4, 14
DRUGS CAN INFLUENCE NEUROTRANSMITTER ACTION
• Agonists – accentuate neurotransmission
• Antagonists – suppress neurotransmission
• Neurotransmitter analogs are used as nuclear medicine tracers (i.e. 2-deoxy-glucose)
Tuesday, November 4, 14
DRUGS AFFECTING NEUROTRANSMISSION
Tuesday, November 4, 14
DRUG EFFECTS ON ACTION POTENTIAL
Tuesday, November 4, 14
Tuesday, November 4, 14
Tuesday, November 4, 14
Nicotine and cancer
(www.wikipedia.com)
Tuesday, November 4, 14
Tuesday, November 4, 14
Tuesday, November 4, 14
Tuesday, November 4, 14