Intro to Neuroscience Cheat Sheet (DRAFT) by Varda

Cellular Components of the nervous system
Neurons
- Dendrites and axon's are wrapped with myelin
- Synapse - Commun­ication point

CNS - Myelin sheath- Oligod­end­rocytes
PNS - Myelin Sheath - Schwann Cells
Cajal- Neurons are polarized establ­ishing direct­ional flow reflected by molecular specia­liz­ations.

Neurons
- Protein synthesis occurs in the soma
- Long axon with a terminal where synaptic vesicles release neurot­ran­smi­tters <- presyn­aptic cells
-Posts­ynaptic cells have receptors
Divergence - Few to many
Conver­gence - Many to few

Glia Cells
CNS - Brain + Spinal Cord
- Astrocytes - blood-­brain barrier + buffer ions/n­eur­otr­ans­mitters
- Oligod­end­rocytes - myelinate neuronal axons
-Microglia - macrophage activity + secrete cytokines
PNS - Extension of CNS
- Schwann cells - myelinate neuronal axons + partic­ipate in recovery of function resulting from neuronal damage

Afferent - towards the CNS Efferent- Away from the CNS

Signals can be excita­tory, Inhibitory or Modulatory
Input-­output geometry
- tap - Sensory neuron excites and inhibits motor neuron - Motor conducts action potential causing contra­ction - Flexor relaxes due to inhibition - Leg extends

Optoge­netics - Genes introd­uced, monitor and control activity to light signals by chemical signals


Organi­zation by type of info - Unity of function

Topogr­aphic Maps - Parallel Pathways
Comput­ational Map - Time/order of input

Lesion Studies - direction of inform­ation flow
- Transgenic reporter - specific genes
- Aintibody labeling - specific proteins
- In Situ hybrid­ization - localizing mRNA - particular protein

Receptive Field - region in sensory space where a neuron will respond

Organi­zation of HNS
- Visceral Motor Neurons - synapse with peripheral motor neurons in autonomic ganglion
- Sympat­hetic division: originate at Sympat­hetic trunk at thoracic and lumbar levels
- Parasy­mpa­thetic division - orig @ brainstem and sacral levels
- Enteric division: Gastro­int­estinal tract

- Gray Matter : Cell Bodies
- White Matter : Myelin­-co­vered axon tracts BRAIN - Commis­sures SPINAL CORD - Columns

Genomics - analysis of the complete DNA seq of specie­s/i­ndi­vidual

Homozy­gosity Mapping - Identify multiple genes associated with disorders - Indivi­dua­l/f­amily
Genome­-wide associ­ation studies - Analysis in inheri­tance of large cohorts

Transgenic animals - introduce novel gene into stem/z­ygote cells
Knock-­in/out
-Homol­ogous recomb­ination - Recomb­ining DNA sequence into genome
-Condi­tional Mutations - preventing mRNA becoming protein
- Gene Editing - CRISPE­R-Cas9 - Specific mutations into gene

Electrical Signals of a Neve Cells
Concen­tration gradients from charged protein molecules and ions create a measurable electrical gradient.
electrical gradient - potential difference across the cell membrane.

Resting membrane - constant voltage at cell rest (-40_-90)
Synaptic potential - Change in potential one neuron stimulates another via synapses using a neurot­ran­smitter
Action Potential - Nerve impuls­e/spike travels along an axon

Passive electrical response - no response to the membrane potential
Hyperp­ola­riz­ation - stimulus casing the membrane to go negative than the resting potential
Active electrical response - stimulus causing the membrane potential to increase past threshold - depola­rizing action potential

Stimilus intensity - Action potential frequency

Requir­ements for Generating Cellular electrical signals
1. Concen­tration gradient
2. Membrane semipe­rme­ability through ion channels

Nerst equation linear relati­onship between transm­embrane concen­tration gradient + membrane potential
- predicts the electrical potential at electr­och­emical equili­brium for 1 ion.

Resting membrane is more permeable to K+ than any other ion

During depola­riz­ation - membrane potential becomes more positive
During repola­riz­ation - membrane potential becomes more negative

Rising phase, overshoot phase, falling phase, undershoot phase

Chapter 3 - Voltag­e-D­epe­ndent Membrane Permea­bility

At rest, neuronal membranes are more permeable to K+, than to Na+, the resting membrane potential is negative and approaches the equili­brium potential for K+.
During an AP, the membrane becomes permeable to Na+, the MP becomes positive and approaches the equili­brium potential for Na+

MP and Permea­bility change affect each other
axon membrane permea­bility is voltag­e-d­epe­ndent
By examining how the inward and outward currents changed, it is possible to measure ion permea­bility as the membrane potential varied.

Chapter 4 - Ion Channels and Transp­orters

Measur­ement of currents flowing through single ion channels
Ion channels and the currents flowing through them should have several properties :
- capable of allowing ions to move across the membranes at high rates
- make use of the electr­och­emical gradients of various ions
- channels select­ivity
- sense changes in membrane potential

The Patch Clamp Method
Four config­ura­tions in patch clamp measur­ements of ion currents
Cell-a­ttached recording.
Whole-cell recording.
Inside-out recording.
Outsid­e-out recording

Patch clamp measur­ements of ion currents can separate currents through individual channels (micro­scopic currents) or many channels (macro­scopic currents) repres­enting relatively large surfaces of membrane.
Micros­copic and macros­copic currents have also been shown for single K+ channels

Channels for both Na+ and K+ are voltag­e-gated
- They open during depola­riz­ation, but at different times
- They close during a hyperp­ola­riz­ation
- The gates of both channels are closed when the membrane potential is hyperp­ola­rized


Tetrod­otoxin, saxitoxin, μ-Cono­toxin – block Na+ channels; inhibit depola­riz­ation.
α-Toxins – prolong the action potent­ials, scrambling inform­ation flow.
β-Toxins – Cause Na+ channels to open at lower-­tha­n-n­ormal potent­ials, causing uncont­rolled action potential firing.
Batrac­hotoxin – removes inacti­vation and shifts activation of Na+ channels.
Dendro­toxin, apamin, charyb­dotoxin block K+ channels

Voltag­e-gated ion channels:
SCN - Na+ channel genes.
KCN – K+ channel genes.
CACNA – Ca2+ channel genes.
CLCN – Cl- channel genes

Ligand­-gated ion channels genes:
Neurot­ran­smi­tte­r-g­ated.
Cyclic nucleo­tid­e-g­ated.
Transient receptor potential family of genes.
Thermo­sen­sitive channel.
Mechan­ose­nsitive channel.

Chapter 5 - Synaptic Transm­ission
- Chemical synapses.
Use neurot­ran­smi­tters and their receptors.
Ca2+-d­epe­ndent neurot­ran­smitter release
Unidir­ect­ional.
Slower.
- Electrical synapses
Uses gap junctions as ion channels.
Bidire­cti­onal.
Faster.

A presyn­aptic terminal button (top) forms a synapse with a postsy­naptic dendrite (bottom).



Generation of action potentials in one neuron results in the synchr­onized firing of action potentials in the adjacent neuron

Hippoc­ampal intern­eurons – one of the few places in the CNS that use electrical synapses

Entails electrical (action potential in presyn­aptic neuron), chemical (neuro­tra­nsm­itter diffusing across the synaptic cleft), and then resumption of electrical (action potential in postsy­naptic neuron) transm­ission
Ultima­tely, action potential in the postsy­naptic neuron is generated by the opening of ion channels, thereby changing the membrane potential.
- Achieved through either ionotropic or metabo­tropic receptors


Presyn­aptic struct­ures:
filame­ntous structures help guide vesicles to active zone.
Several pools of vesicles exist: only those at the active zone are ready for exocyt­osis.

Postsy­naptic struct­ures:
Postsy­naptic Density (PSD)
helps anchor postsy­naptic receptors in postsy­naptic membrane: prevents lateral diffusion of receptors.
Contains many proteins involved in plasti­cit­y-d­epe­ndent processes, such as learning, memory, health, and disease

Quantal* release of neurot­ran­smi­tters.
Synaptic transm­ission at the neurom­uscular junction (nmj) results in end-plate potentials (EPP) in the muscle cell.
Acetyl­choline is released in discrete packets, each leads to a miniature EPP (MEPP).
Sponta­neous firings in the muscle cell manifested in MEPPs (Fatt and Katz, 1952).A quantum (plural: quanta) is the smallest discrete unit of a phenomenon



Ligand­-gated ion channels.
Receptor itself is also the ion channel.
Also called ionotropic receptors.
Fast: postsy­naptic potentials responses range: 1-2 msec after an action potential reached the presyn­aptic terminal.
Metabo­tropic receptors.
G-prot­ein­-co­upled receptors: G-protein complex activated by ligand binding to the receptor.
Slow: postsy­naptic potentials responses range: hundreds of msec to 1-2 minutes.
Cascade of phosph­ory­lation events and second­-me­ssenger production

Release of transm­itters from synaptic vesicles.
Individual quanta of neurot­ran­smitter released are caused by the fusion of the vesicle membrane with the plasma membrane.
Number of quanta released positively correlated with the number of vesicles fusing.
The average synaptic vesicle has a diameter of ~ 50 nm, corres­ponding to about 100 mM acetyl­choline

Local recycling of synaptic vesicles.
Following neurot­ran­smitter exocyt­osis, fusion of synaptic vesicles with the plasma membrane is temporary.
Retrieved vesicular membrane passes through several intrac­ellular compar­tments, such as endosomes.
Vesicles are loaded with neurot­ran­smitter in an ATP-de­pen­den­t/p­roton antiporter process.
Vesicles are stored in the presyn­aptic reserve pool until needed again to partic­ipate in neurot­ran­smitter release.

SNARE Complex at Work to Exocytose Neurot­ran­smi­tter.
Key Proteins:
Vesicular (V-SNARE) proteins: synapt­obr­evin, synapt­ota­gmin.
Target (T-SNARE) proteins: syntaxin, SNAP-25.
Synapt­obrevin coils around syntaxin and SNAP-25.
Synapt­otagmin binds Ca2+  confor­mat­ional change to pull vesicle closer to plasma membrane, which protrudes towards the former, bringing the 2 membranes closer together.
Fusion of the 2 membranes leads to exocytosis of neurot­ran­smitter

Myasthenic Syndromes – abnormal transm­ission at neurom­uscular synapses.


Concepts 5.3, 5.4, 5.6, and 5.7 will not be covered in this course.

Chapter 6 - Neurot­ran­smi­tters and Their Receptors

Neurot­ran­smi­tters :
- In the presyn­aptic neuron
- Must be released during synaptic activity
- binds to receptors on the post synaptic neuron

Types - Neurop­eptides or peptide neurot­ran­smi­tters, Small molecule neurot­ran­smi­tters - acetyl­cho­line, amino acids, purines, and biogenic amines.