Chapter 2, Structure and Function of the Nervous System Flashcards
Neuron structure includes:
- Dendrites: receiving
- Cell body: collecting / summing
- Axon: sending
Convergence
Each neuron
receives/integrates information from
many cells
Divergence
Information may be
transmitted to a few or thousands of
other neurons
Dendrites
- Dendrites are covered in spines
- Dendrites and spines are constantly modified and can change rapidly
Soma
- The soma, or cell body, performs most metabolic functions
- Many proteins and neurotransmitters are created in the soma
and then must be transported
Axon
- The myelin sheath protects the axon and increases speed of conduction along the axon
- Schwann cells in PNS
Oligodendroglia in CNS - Nodes of Ranvier are breaks in the myelin sheath; sites where APs are regenerated
Resting Potential
- The resting potential of the cell is caused by the distribution of ions inside and outside the neuron
Local Potentials
- Local potentials, or graded potentials, are small, transient changes in membrane potential
- Depolarization (Na+ flows in)
- Hyperpolarization (Cl-flows in)
- Summation (integration) is possible
- Integration of EPSPs and IPSPs at the axon hillock
- When summation reaches threshold (-50mV), an AP is triggered
Action Potenial Phases
- A basic AP has the following phases:
- Rising phase, overshoot, falling phase, undershoot
Action Potential
- The AP has an absolute refractory period because of the inactivation of voltage-gated Na+ channels
- Some drugs alter action potential conductance by blocking the voltage-gated Na+ channels.
- What would these drugs be used for?
- Other drugs alter the action potential by binding to closed Na+ channels
- What would these drugs be used for?
Novocain
- Novocain inhibits the voltage-gated Na+ channels, which prevents APs from being generated
- Used in dental work to prevent pain
Examples of natural toxins that can be used experimentally to alter the Na+ channels
- Pufferfish tetrodotoxin (TTX) – clogs Na+-permeable pore
- Red tide saxitoxin – blocks Na+ channels
Characteristics of Local Potentials
- Graded
- Decremental
- Spatial and temporal summation
- Produced by opening ligand-gated channels
- Depolarization or hyperpolarization
Characteristics of Action Potentials
- All-or-none
- Nondecremental
- Intensity of stimulus coded by rate of firing
- Produced by the opening of voltage-gated channels
- Depolarization
Types of Synaptic Connections
- The most common is axodendritic, but many types of synaptic connections are possible
1. Axodendritic
2. Axosomatic
3. Axoaxonic - Small axons may only have one
active zone - Larger synapses have more active
zones - One axon terminal may contact
multiple postsynaptic cells
Structure of Synapses
- Presynaptic cell: Synaptic vesicles
- Synaptic cleft
- Postsynaptic cell: Dendritic spine, Postsynaptic density: Area of the dendritic membrane facing the synaptic cleft with many neurotransmitter receptors.
Criteria for a chemical to be considered a neurotransmitter:
- Presynaptic cell contains the chemical plus a mechanism to make it.
- A mechanism for inactivating the chemical should also be present.
- Chemical is released from the axon terminal when a neuron is stimulated.
- Receptors for the chemical are present in the postsynaptic cells.
- Direct application of chemicals or agonists has the same effect on postsynaptic cells as stimulating the presynaptic neuron.
* Applying an antagonist that blocks the receptors inhibits both the chemical’s action and the effect of stimulating the presynaptic neuron.
Major neurotransmitter classes
Classical neurotransmitters
* Amino acids
* Monoamines
* Acetylcholine (Ach) Purines
Nonclassical neurotransmitters
* Neuropeptides
* Lipids
* Gases
Examples of Amino Acids
- Glutamate
- GABA
- Glycine
Examples of Monoamines
- Dopamine (DA)
- Norepinephrine (NE)
- Serotonin (5-HT)
- Histamine (HA)
Examples of Acetylcholine (Ach) Purines
- Adenosine triphosphate (ATP)
- Adenosine
Examples of Neuropeptides
- Endorphins and enkephalins
- Corticotropin- releasing factor (CRF)
- Orexin/hypocretin
- Brain-derived neurotrophic factor (BDNF)
Examples of Lipids
- Anandamide
- 2-Arachidonoylglycerol
Examples of Gases
- nitric oxide (NO)
- Carbon monoxide (CO)
- Hydrogen sulfide (H2S) (small 2)
The steps of neurotransmission
- Synthesis & storage
- Release
- Receptor Action
- Inactivation
Neurotransmitter Synthesis
- Most neurotransmitters are made in the axon terminals; enzymes for their synthesis are transferred to the terminals.
- Neuropeptides are made from protein precursors. Precursors are shipped from the cell body to axon terminals in large vesicles. Replenishment is thus slower than for small molecules.
Neurotransmitter Storage
- An individual neuron can make one or several neurotransmitters
- Vesicles can hold one or more types of transmitters
Neurotransmitter Release
- Neurotransmitter release is regulated by:
- Rate of neuron firing;
- The probability that vesicles will undergo exocytosis;
- Autoreceptors, which are receptors for the same transmitter released by the neuron.
Neurotransmitter Inactivation
- Reuptake
- Diffusion
- Enzymatic degradation
- Re-uptake by glial cell (glutamate only)
How cocaine disrupts neurotransmission
- Cocaine blocks transporters for DA (as well as 5-HT and NE)
- DA cannot be inactivated and thus stays in the synapse
Lipid and Gaseous Transmitters
- Lipid and gaseous transmitters are not stored in nor released from synaptic vesicles
- Synthesized on demand by postsynaptic cell
- Act as retrograde messengers on the presynaptic cell, and also diffuse to other neurons
Neurotransmitter Receptors
- NT receptors are proteins located on cell membranes
- NTs bind to more than on type of receptor type
- The effect of receptor activation may be excitatory or inhibitory
- Drugs can be designed to affect specific receptor subtypes
Ionotropic Receptors
- Contain a pore that allow ions to pass through when open
- Opens pore in response to NT binding
- Fast to respond
- Effects are brief
- Made of 4-5 subunits with a pore (an ion channel) in the centre
- The pore matters
- Some receptors are Na+ channels à excitatory response
- Others are Cl- channels à inhibitory response
Metabotropic Receptors
- No pore
- Activates G protein in response to NT binding
- Relatively slow
- Effects can be long lasting
- More possibilities for what can happen
- Made of a single protein subunit with 7 transmembrane domains
- AKA G-protein coupled receptor
- Made of a single protein subunit
with 7 transmembrane domains - AKA G-protein coupled receptor
- G proteins can
- Inhibit or activate ion channels
- Stimulate or inhibit effector enzymes in
the cell membrane that synthesize or
break down second messenger
molecules
Some second messengers:
* Cyclic adenosine monophosphate
(cAMP) – stimulates protein
kinase A (PKA)
* Cyclic guanosine monophosphate
(cGMP) – stimulates protein
kinase G
* Phosphoinositide – stimulates
protein kinase C (PKC)
* Ca2+ can act as a 2nd messenger
– stimulates calcium/calmodulin
kinase II (CaMKII)
Binding Sites
- All receptors have binding sites for neurotransmitters
- Many receptors have additional binding sites, called allosteric sites which modify (positively or negatively) the effects of an agonist
Synaptic Plasticity
- Functional and structural synaptic changes including change in strength, growth of new synapses, growth of axon terminals, dendrites, spines, etc.
Examples of plasticity:
* Plasticity in development (pruning is normal)
* Learning and memory
Many neurological disorders are associated with abnormal
spines
Synaptic change can result from sensory/environmental stimuli,
and from psychoactive drugs—especially with repeated
exposure
Hormones vs. Neurotransmitters
Endocrine communication is different than synaptic
transmission but… The same substance can act as both an NT
and a hormone
Cholinergic Projections
Noradrenergic Projections
Dopaminergic Projections
Serotonergic Projections
