Unit 1 Flashcards
Information comes into the neuron from projections called
Axons
The junctions through which information passes from one neuron to another are called
Synapses
Presynaptic neurons release molecules called ________ to signal onto postsynaptic neurons
neurotransmitters
Glia
Non-neuronal cells
CNS contains
Astrocytes, oligodendrocytes, microglia, and ependyma
PNS contains
Satellite and Schwann cells
CNS Is composed of
brain and spinal cord
PNS is composed of
nerves
Neuron
specialized cells that conduct and process information, enabling thought, perception, and control of movement
Action Potential
signals are transmitted by a change of membrane voltage within a neuron
Neurotransmitters are
chemicals
Synaptic plasticity
The strength of synaptic connections can be modified by neuronal activity
Neuronal membrane
Barrier
Soma
cell body
Axon
sends information
Dendrite
receives information; “antennae” of neurons
Synapse
communication sites between neurons
Neuronal Membrane thickness
5 nanometers (nm)
Neuronal Membrane is composed of
phospholipid bilayer that is hydrophilic on outside, and hydrophobic on inside
Neuronal Soma size
5-50 micrometers μm
Cytosol
watery fluid inside the cell
Organelles are
membrane-enclosed structures within soma
What are the organelles inside the soma
Ribosomes, endoplasmic reticulum, golgi apparatus, mitochondria
Ribosomes
major site for protein synthesis
Endoplasmic Reticulum & Golgi Apparatus
sits for sorting proteins for delivery to different cell regions
Mitochondria
site for cellular respiration/generating ATP
Cytoplasm
contents within a cell membrane, excluding the nucleus
Nucleus
contains DNA, is the site for gene expression, transcription and RNA processing
Cytoskeleton
supports the cell shape; internal scaffolding
Cytoskeleton consists of
Microtubules, neurofilaments, microfilaments
Microtubules
20 nm, largest diameter, tubulin based
Neurofilaments
10nm, intermediate diameter
Microfilaments
5 nm, smallest diameter, actin based
Microtubules are located in
Dendrites & axons
Neurofilaments are located in
Axon & soma
Microfilaments are located in
the lining of the entire cell
Axon length
Up to 1 meter
Axon hillock
Beginning
Axon terminal
end
Differences between cytoplasm of axon terminal and axon
- no microtubules in terminal
- presence of synaptic vesicles in terminal
- abundance of membrane proteins
- large number of mitochondria
Signal transformation
electrical –> chemical –> electrical
Dendritic spines
postsynaptic sites, receiving signals from axon terminals
Projection neurons
- Principal neurons
- send an axon out of where the somata are located
Intrinsic neurons
- Interneurons
- make synapses within the structure where their soma is located
Cortex
80% are projection neurons with majority being pyramidal neurons
Cerebellum
Purkinje cells (projection); granule cells (interneuron)
Retina
Retinal ganglion cells (projection); bipolar cells (interneuron)
Cell type
defines a group of neurons that carry out a distinct task
Intracellular and extracellular fluids contain
water and ions
Membrane potential
the voltage across the cell membrane at any moment
Resting membrane potential
the membrane potential when the neuron is not “excited” or “fired”
In neurons, the value of the resting membrane potential is between
-40 mV and -90 mV
Steps of electrophysiology
- insert a microelectrode into the cell
- connect microelectrode to voltmeter which measures the potential cell difference between inside and outside the cell
3 factors for resting membrane potential
- intracellular potassium concentration is HIGH
- extracellular potassium concentration is LOW
- cell membrane is selectively permeable to potassium ions
*sodium is the opposite
The Nernst equation calculates
the equilibrium potential for an ion (the electrical potential that exactly balances a concentration gradient for that ion)
Neuronal membranes are permeable to more than one type of ion true or false
True
Goldman equation considers
the membrane permeability of various ions
Goldman equation describes a _________ condition that is a __________ among several equilibrium potentials.
steady-state ; “compromise”
Hyperpolarization
a change in membrane potential that makes the inside of the cell more negative
Depolarization
a change that makes the inside of the cell less negative
Discovered action potential
Sir John Eccles, Alan Lloyd Hodgkin, Andrew Huxley
Voltage-gated ion channel steps
- Transmembrane
- Ion Selectivity
- Open states depend on depolarization
Voltage-Gated Sodium Channel
- open fast
- open for a short period
- inactivate during prolonged depolarization (cannot be opened again immediately by depolarization)
Voltage-Gated Potassium Channel
- open slow
- stay open for longer
- do NOT inactivate
Tetrodoxin (TTX)
- puffer fish
- Clogs Na+ permeable pores
- Blocks all sodium-dependent action potentials
- lethal dose is 0.33 mg/kg
Batrachotoxin
- poison dart frogs
- blocks inactivation so channels remain open
Aconitine
- Flower buttercups
- Blocks inactivation so channels remain open
Threshold
The level of depolarization that must be reached in order to trigger an action potential
Action potential generation is the
process by which a neuron rapidly depolarizes from a negative resting potential to a more positive potential
Action potential generation is achieved by
the movement of ions through voltage-gated ion channels
- Resting state
- the initial membrane potential is -70mv
- both voltage-gated NA and K channels are closed
Steps of generating action potential
- Resting State
- Depolarization
- Rising phase
- Falling phase
- Undershoot
- Depolarization
- membrane becomes depolarized
- NA+ channels open and Na+ enters the cell
- if threshold is reached, action potential is triggered
Repolarization
the efflux of K+ ions across the membrane
- Rising Phase
- Na+ ions flood into the cell and membrane moves toward equilibrium potential (60mV)
- Does not get that high because Na+ channels close fast
- Falling Phase
- although Na+ channels are inactivated, K+ channels open
- K+ ions flood out of the cell and repolarize the membrane
- Undershoot
- K+ channels are open long enough for membrane potential to get near equilibrium potential
Myelin
Layers of myelin sheath facilitate action potential propagation
Voltage-gated ion channels are concentrated at the
Node of Ranvier
Saltatory Conduction
Jump
Presynaptic cell
- Mitochondria provide energy
- Synaptic vesicles contain neurotransmitters
Postsynaptic cell
- neurotransmitter receptors located on the membrane
Synaptic Cleft
A gap between synapses that is 20nm wide
Synapses between neurons
- axospinous
- axodendritic
- axosomatic
- axoaxonic
Synapses between neuron and muscle
neuromuscular junction
Axospinous
axon to dendritic spine
Axodendritic
Axon to dendrite
Axosomatic
Axon to cell body
Axoaxonic
axon to axon
Neuromuscular junction
axon to muscle
Step of neurotransmitter release via exocytosis
- vesicle containing neurotransmitter
- plasma membrane depolarizes at axon terminal. voltage-gated Ca2+ channels open and it Ca2+ diffuses into cell
- Ca2+ influx makes syn. vesicles fuse w presyn. membrane and the neurotransmitter is released into synaptic cleft by exocytosis
- synaptic vesicle recycled by endocytosis
Gap-Junction channels
allow information to be transferred directly (because anything is allowed to flow through, not just certain ions)
Electrical Synapses
- cells are electrically coupled by gap junction
- bidirectional transmission
- fast transmission (membrane potentials change instantaneously)
Psychiatric disorder targeted neurotransmitters
Dopamine & Serotonin
Most common excitatory neurotransmitter
Glutamate
Adrenaline
Fight or flight neurotransmitter
Noradrenaline
Concentration neurotransmitter
Glutamate
Memory neurotransmitter
Dopamine
Pleasure neurotransmitter
Serotonin
Mood neurotransmitter
Most common inhibitory neurotransmitter
GABA
GABA
Calming neurotransmitter
Acetylcholine
Learning neurotransmitter
Endorphins
Euphoria neurotransmitter
2 classes of neurotransmitters
- small molecule
- peptide neurotransmitters AKA neuropeptides
Small molecule neurotransmitters
- Amino Acids: Glutamate, aspartate, GABA, glycine
- Acetylcholine
- Biogenic Amines: Dopamine, serotonin (5-HT), norepinephrine, epinephrine, histamine
Peptide neurotransmitters (neuropeptides)
- Bran-gut peptides: Substance P
- Opioid peptides
- Pituitary peptides
- hypothalamic-releasing peptides
- others
2 classes of neurotransmitter receptors
Ionotropic & metabotropic
Ionotropic receptors
Ligand-gated ion channels
Metabotropic receptors
activate second-messenger systems
Ionotropic receptor excitatory effects
Na+ diffuses into postsynaptic cell and depolarizes the membrane towards the action potential threshold
Ionotropic receptor inhibitory effects
- Cl- moves into postsynaptic cell and leads to hyperpolarization
- K+ moves out of postsynaptic cell and leads to hyperpolarization
What determines the action of GABA to be inhibitory?
Concentration gradient
Can GABA be excitatory?
Yes, if the Cl- concentration is higher inside the cell than outside. When channels open, Cl- ions flow out
*temporarily excitatory in newborns
G-Protein Coupled Receptor steps
- Binding of the neurotransmitter to the receptor protein
- Activation of G-protein
- G-protein splits into two parts: Gα & Gβγ
- Activation of effector systems, including ion channels and enzymes
Synaptic Integration
- a process by which multiple synaptic potentials combine with one postsynaptic cell
- Most CNS neurons receive thousands of synaptic inputs.
Plasticity
Capacity of the nervous system to change
Temporal Features of plasticity
Short Term: from milliseconds to seconds to minutes
Long Term: from minutes to hours to days to life-time
Spatial Features of plasticity
- At synapses (synaptic plasticity)
- Within neurons
- Within glia
Plasticity affects the _____________ of neural circuits and systems
structure and function
Plasticity is the foundation of
- Learning and memory
- Recovery from injury or disability
- Pathology
Specificity
Only active synapses are strengthened
Associativity
Co-active synapses are strengthened
AMPA and NMDA receptors are
Glutamate-gated cation channels (Na+, K+)
2 unique properties of NMDA receptors
1.voltage-gated owing to action of Mg2+
2. Conducts Ca2+
Glutamate receptors mediate excitatory synaptic transmission with
AMPA & NMDA receptors
Increase in intracellular Ca2+ triggers
- activation of kinases
- phosphorylation of AMPA receptors to increase the Na+ conductance
- insertion of additional AMPA receptors
What happens if there is no AMPA, only NMDA?
No change. The cell won’t become depolarized and trigger the voltage gates, so the Mg2+ wont be removed
Silent Synapse
a synapse where an excitatory postsynaptic response is absent at the resting membrane potential becomes apparent on depolarization
Maturation of silent synapses
- Developmentally regulated
- LTP
Molecular Mechanisms of LTD
- Glutamate receptors mediate excitatory synaptic transmission (AMPA receptors and NMDA receptors)
- Moderate intracellular Ca2+ increase triggers second messenger systems
1- activation of phosphatases- dephosphorylation of proteins
- internalization of AMPA receptors
Hebbian Rule (Hebb’s Postulate)
When axon of cell A is near enough to excite cell B and repeatedly or persistently take part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of cells firing B, is increased
Critical Period
Time during early postnatal life when the development and maturation of functional properties of the brain, its ‘plasticity’, is strongly dependent on experience or environmental influences
What happens to synaptic connections during a critical period
Correlated patterns of activity are thoughtful to mediate critical periods by stabilizing concurrently active synaptic connections and weakening or eliminating connections whose activity is divergent
How do we know there is a critical period?
The complete absence of certain experiences during critical periods prevents the development of associated brain functions
Protoplasmic astrocytes
- Exist in grey matter
- Bushy appearance with highly arborized short processes
Fibrous astrocytes
- exist in white matter
- elongated appearance with long and less complex processes
Morphogenesis of astrocytes during postnatal development
- Long major branches invade the domains of neighboring astrocytes
- Ramification into smaller processes increases while the domain invasion reduces
- Acquisition of complex morphologies within distinct domains
Astrocytes are coupled together via ________ at the tips of astrocyte processes
gap junctions
Astrocyte gap junctions facilitate
intercellular synchronization and perform important homeostatic roles
The brain paradox
- The brain requires continuous energy but lacks fuel stores
- The brain uses glucose as its main source of energy, which comes from the circulatory system
- Most brain energy is used at synapses to sustain the effective and rapid transfer of information
Astrocyte Function
- maintenance of ion homeostasis
- neurotransmitter uptake and recycling
- synaptogenesis during early postnatal development
- synapse removal and maturation
- regulation of blood flow during
Astrocyte intracellular Ca2+ signaling
- astrocytes do not generate or propagate action potentials
- astrocytes are proposed to regulate neurons via intracellular Ca2+-dependent signaling
How silencing astrocyte Ca2+ signaling alters behavior
signaling astrocyte Ca2+ signaling in the striatum changes neuronal activities and results in behavioral alterations resembling obsessive-compulsive disorder
Reactive astrocytes
astrocytes that undergo morphological, molecular, and functional changes in response to pathological situations in surrounding tissue (due to CNS disease, injury, deleterious experimental manipulation)
Changes in gene expression, morphology, metabolism, and physiology result in
gain of new function(s) or loss of homeostatic ones
Moderate astrocyte reactivity
astrocytes become hypertrophic, territories of processes do not overlap
Severe astrocyte reactivity
Astrocytes from glial scars with extensive overlap of processes
Protective aspects of reactive astrocytes
- homeostatic support
- release of growth factors
- phagocytosis of debris
Detrimental aspects of reactive astrocytes
- release of cytokines
- oxidative stress
- synaptic damage
Huntington’s Disease (HD)
a neurodegenerative disorder caused by a defect in the Huntingtin gene
Cytosol is the watery fluid inside the cell of a neuron enclosed by a neuronal membrane. What is the composition of the cytosol?
Potassium-rich solution
What does cell theory state?
The elementary functional unit of all animal tissues is the individual cell?
A neuron establishes a resting membrane potential under the condition where intracellular K+ concentration is ~150 nM, while extracellular K+ concentration is ~5nM. How does the membrane potential of this neuron change when extracellular K+ concentration is artificially elevated to 50 nM?
Depolarization because less potassium diffuses out of the neuron
Charge on the inside of the cell membrane during resting membrane potential
The cytosol along the inside surface of the cell membrane has a negative charge compared to the outside
Why are action potentials “all or none”?
depolarizing the neuronal membrane has no effect until the membrane potential crosses a threshold
What does the myelin sheath consist of?
many layers of membrane provided by oligodendrocytes
What is synaptic transmission
The process of information transfer at a synapse
Into what categories are neurotransmitter receptors classified?
transmitter-gated ion channels & G-protein-coupled receptors
What does Hebb’s postulate refer to?
Synaptic rearrangements that occur in response to simultaneous presynaptic and postsynaptic activity
True or false, microglia only function under pathological conditions
False
The Nernst equation and Goldman equation
calculate the equilibrium potential for specific ions and the resting membrane potential
Action potential is explained by
The voltage and time-dependent changes in the permeability of the neuronal membrane to Na+ and K+
Type I Oligodendrocyte
- small, rounded cell body
- high number of very fine processes emerging in multiple directions
- present in grey AND white matter
Type II Oligodendrocyte
- polygonal shape
- fewer and thicker processes directed toward axons
- Present in WHITE matter
Type III Oligodendrocyte
- bulky cell body
- one to four processes directed toward axons
- present in WHITE matter
Type IV Oligodendrocyte
- elongated cell body
- adhere and extend to medium or large axons
- present in WHITE matter
Myelin is composed of
Lipids, water, and proteins
2 coordinated motions that myelin grows in:
- lateral extension of myeline membrane layers toward the nodal region
- Wrapping of leading edge at the innermost tongue
The 3 myelin waves of rapid synchronized change are
- early adolescence
- adolescence
- aging
Oligodendrocyte Progenitor Cells (OPCs) are located in the:
- developing brain
- mature circuits
OPCs can turn into
myelinating Oligodendrocytes
Intrinsic Myelination
- activity-independent
- OPCs guide Oligodendrocyte differentiation and myelination of axons using encoded programs
Adaptive Myelination
- activity-dependent
- size and number of myelin sheaths are modified by neuronal activity
Existing Oligodendrocytes undergo ___________ to alter sheath length and thickness and generate new sheaths
Plasticity
Functions of Oligodendrocytes in CNS
- Myelination of axons
- Regulation of ion channel expression at node of ranvier
- Maturation and maintenance of the node of Ranvier
- Modulation of neuronal excitability and neurotransmitter release
- Metabolic support to axons and ion homeostatic maintenance
Remyelination
The regenerative process by which myelin sheaths are restored to demyelinated axons
Axonal Degeneration
the process of destruction of axons that results in the loss of neuronal communications
Microglia are derived from
progenitor cells in the yolk sac
Neurons, astrocytes, and oligodendrocytes originate from a
common lineage of neural stem cells within the neuroectoderm
Resting (surveillant) microglia characteristics
- ramified morphology
- physiological condition
Activated microglia characteristics
- swollen morphology with larger cell body and shorter, thicker processes
- during development and pathological condition
Synaptic pruning is
the process of synapse elimination during early childhood until early adulthood
