Midterm 1 Flashcards
Why are animals used in research?
Can provide info about origins/mechanisms of human physiology/behaviour. Can control development/learning history, as well as easily take neural tissue.
What is the difference between a model organism and an animal model?
Animal models also include the manipulations of the model (ex. disease state/cognitive domain).
What are neurons?
Highly specialized cells (contain features in other cells) that transmit info via electrical/chemical means. Carry electrical signals that modulate chemical signals.
What are glial cells?
Regulate speed of neural signals/synaptic activity; help maintain neural health/architecture; extra-synaptic channel regulation.
Who was Camillo Golgi?
He advocated the “Reticular Theory” (nerve cells directly connected). Discovered “Golgi apparatus”. Developed “Golgi Stain” (provided evidence for “Neuron Doctrine”), help follow processes.
Who was Santiago Ramón y Cajal?
Advocated the “Neuron Doctrine” (neurons are discrete entities that communicate using special contacts). Used Golgi staining and light microscopy.
Who was Charles Sherrington?
Studied the transfer of electrical signals in reflex pathways; named “synapses”.
What is the axon’s function?
Transmit info via electrical signals
What are dendrites?
Form the postsynapse. Can be extensively branched or almost absent. More SA = more synaptic inputs. Receive information.
How does information flow within a neuron?
From dendrite to cell body to axon
What is an action potential?
Self-regenerating wave of electrical activity along axon; rapid change in electrical potential across membrane; “All or nothing”.
What is the purpose of myelin?
Insulation, maintain speed and prevent back propagation of signal.
What is the difference between interneurons and projection neurons?
Interneurons are very small, and stay within one structure (tend to be inhibitory). Projection neurons target areas outside of structure in which the soma reside (tend to be excitatory).
What is the difference between an oligodendrocyte and a Schwann cell?
They are both living cells that myelinate axons. Oligodendrocytes are in the CNS, and Schwann cells are in the PNS. Oligodendrocytes can myelinate at multiple locations at once (on the same or different axons), while Schwann cells can only myelinate a single site.
What are the nodes of ranvier?
They are spaces b/n myelin sheath. They continue the propagation of the electrical signal.
How are signals passed b/n neurons?
Ends of axons secrete neurotransmitters that have been (typically) packaged into vesicles, then they diffuse from the presynapse across the synaptic cleft and bind to receptors on the postsynapse.
What are unipolar neurons?
Only one process from cell body (invertebrates)
What are bipolar neurons?
One axonal process and one dendritic process from cell body - both can branch near termini.
What are pseudounipolar neurons?
Axon bifurcates shortly after leaving soma - dendrites present at terminal end, typically in periphery.
What are multipolar neurons?
Prototypical neuron. Multiple dendrites, only one axonal process (can branch near ends).
What are pyramidal neuron cells?
Excitatory projection neurons, including all cortical output. In hippocampus.
What are retinal cells and how does light travel to the brain?
Eye. Rods and cones -> Retinal bipolar cells -> ganglion cells. Amacrine/horizontal cells provide lateral interactions.
What are ganglia cells?
Nerve cell cluster in autonomic NS and sensory system
What are Purkinje cells?
Found in Purkinje layer of cerebellum. Extensive arborization. Send inhibitory projections deeper into cerebellum. Manage motor coordination.
What are astrocytes?
CNS. Secrete substances that influence new synaptic connections. Some stem-cell like characteristics. Create blood brain barrier around blood vessels.
What are microglial cells?
Similar to microphages. Scavenger cells that remove debris from injury sites/normal cell turnover. Secrete cytokines that modulate local inflammation and influence apoptosis.
What are astrocyte precursors (glial stem cells)?
Found in subventricular zone. More stem cells, neurons, mature astrocytes, oligodendrocytes.
What are oligodendrocyte precursors (glial stem cells)?
Common in white matter. Usually oligodendrocytes, sometimes astrocytes.
What is the difference between apical and basal dendrites?
Apical = top of arbor, basal = proximal to soma
What is convergence?
The integration of multiple synaptic inputs onto a single neuron.
What is divergence?
A single neuron synapsing onto multiple cells.
What is a tripartite synapse?
When an astrocyte releases chemicals that interact with a synapse.
What are afferent neurons?
Carry incoming APs/flow of info from periphery towards CNS (Approach).
What are efferent neurons?
Carry outgoing APs/info away from CNS (Exit)
What are interneurons?
Lie b/n afferent and efferent neurons, and modify nerve signal (often inhibitory)
What are nuclei?
Collection of neuron cell bodies (soma) in a common anatomical unit inside the brain and spinal cord (CNS).
What are ganglia?
Collection of neuron cell bodies (soma) in a common anatomical unit outside brain/spinal cord (PNS)
What is a tract?
An organized bundle of nerve fibres carrying related info from one region in CNS to another
What is a gyrus?
A ridge/fold of cerebral cortex
What is a sulcus?
A valley/crease of cerebral cortex
What is a fissure?
A deep groove used to define lobes and hemispheres
How do signals pass through the spinal cord?
Sensory info carried by spinal nerves enters via dorsal roots of ganglia, and motor commands leave via ventral roots of ganglia.
How do reflexes travel in the knee jerk reaction?
Sensory afferent excites motor neuron, causing contraction of extensor. Also excites inhibitory spinal interneuron, relaxing flexor muscle. This leads to a kick.
What is the function of the 12 cranial nerves?
Emerge directly from forebrain (2) and brainstem (10).
Relay information b/n head/neck and brain.
Each cranial nerve is associated with one or more nuclei in the brain.
What are electrical signals generated on the basis of?
Flow of ions across the membrane.
How are membrane potentials measured?
Microelectrodes connected to voltmeter. records resting membrane potential.
What is the average resting membrane potential?
-40 to -90 mV
What is the electrical potential across cell membranes related to?
Differences in concentrations of charged ions on either side of the membrane
What are electrical signals in nerve cells produced by?
Temporary changes in electric current into and out of the cell, which push the electrical potential away from its resting value.
What is a receptor potential?
Brief activation of sensory receptors causes slight depolarization in membrane potential. Accumulation of receptor potentials can be enough to trigger AP. (Ex. light, sound, heat, touch, pain)
What is a synaptic potential?
Activating a synaptic contact b/n neurons causes slight depolarization in membrane potential. Signal induced in post-synaptic cell. Related to communication from one neuron to another.
What is an action potential?
Electrical signal travels along axon. Sufficiently strong depolarization from synaptic/receptor potentials. Responsible for long-range transmission. “Spike/Impulse”. The only current that passes on information b/n cells.
What happens when threshold potential is reached?
AP is an active response generated; very brief change from -ve to +ve transmembrane potential. Amplitude is independent of stimulation magnitude. “All-or-none”. Intensity is encoded in frequency rather than amplitude.
What is an anion?
Negatively charged ion
What is a cation?
Positively charged ion
What is the resting membrane potential?
Separation of +ve on outside and -ve on inside of membrane.
Why is the overall charge maintained in a resting membrane potential?
Membrane is impermeable to ions. Passive ion channels and active ion pumps maintain potential.
What is the concentration gradient?
Distribution of molecules/particles from high -> low.
What is the electrical gradient?
Difference in charge across a barrier.
What is the electrochemical gradient?
When particles carry electric charge
What is electrochemical equilibrium?
Combination of chemical & electrical gradients equal in magnitude (2 forces found a balance)
What is equilibrium potential?
Occurs for each molecule/particle/ion individually in which electrical gradient is balanced by diffusion gradient
What do ion channels do?
Allow ions to diffuse down concentration gradient. Are selectively permeable to certain ions.
What do active transporters do?
Actively move selected ions against concentration gradient. Create ion concentration gradients.
How does the sodium-potassium pump work?
- Pumps out 3 Na+ for every 2 K+ in
- Induces conformational change (requires energy)
How does passive/subthreshold current move?
Current travels along axon, and decays with distance. Cannot induce neurotransmitter release at synapse. Electrical potential is localized.
How does active/suprathreshold current move?
Wave moves down entire length of axon, and does not decay. AP is induced, and therefore neurotransmitter release at synapse is induced.
What is depolarization?
Inside becomes less -ve (closer to 0)
What is overshoot?
Inside becomes +ve (reversal of polarity)
What is repolarization?
Returning to -ve, towards RMP
What is hyperpolarization?
Inside becomes more -ve than RMP
What are the steps of an action potential?
1 - Resting Membrane Potential
2 - Depolarization/Overshoot (driven by inward Na+, fast)
3 - Repolarization (driven by outward K+, slower)
4 - Hyperpolarization/Undershoot, then Refractory Period
What did Hodgkin and Katz hypothesize?
AP arises bc neuronal membrane becomes temporarily permeable to Na+
How does a Voltage Clamp work?
Electrode measures membrane potential (Vm) and is connected to voltage clamp amplifier.
Amplifier compares potential with desired/command potential.
When Vm is different, clamp amplifier injects current into axon through electrode. Membrane potential = command.
Current flowing back into axon can be measured.
Why is blocking Na+ or K+ important in voltage clamps?
To determine contributions to voltage changes during AP.
How does voltage dependent permeability work?
Voltage clamp depolarizes membrane potential to 0 mV. Instant capacitive current flows, short inward current, and long-lasting outward current.
Can block ion channels (ex. TTX blocks Na+, TEA blocks K+ and BTX opens Na+)
What is saltatory conduction?
The conduction of an AP through myelinated vs unmyelinated axon
How does conductance occur in myelinated axons?
Few to no channels. Myelin seals membrane, stops leakage of charge. Therefore, passive current flows further/faster with myelin.
How does conductance occur in the Nodes of Ranvier?
There is a high concentration of Na+ channels. Perpetuates AP. Passive current conduction b/n nodes is faster than voltage gated Na+ currents - AP ‘jumps’ from node to node.
What is Multiple Sclerosis?
Gradual degradation of myelin in CNS, reducing capacity to conduct APs. Neuron-axonal pathology. T-cell mediated autoimmune process (attacks oligodendrocytes).
How is MS treated?
Immunomodulating medications.
How does cell-attached recording using the patch clamp method work?
Pipette forms tight seal w/ membrane. Allows experimental control of potential. Isolate single ion channels, change external environment.
How does whole-cell recording w/ patch clamp work?
Suction allows pipette to be continuous w/ cytoplasm. Measurement of potentials from entire cell. Diffusional exchange, can inject substances to the interior of the cell.
How does inside-out recording w/ patch clamp work?
Retracting cell-attached pipette to remove small vesicle w/ intracellular surface exposed. Measurements of current flow w/ modification of intracellular surface medium.
How does outside-out recording w/ patch clamp work?
Retracting whole-cell pipette to expose extracellular surface. Modify medium of extracellular surface to measure.
What did the cell-attached patch clamp reveal about Na+ channels?
Most Na+ channels open in first 1-2ms following depolarization (there is a inactivation gate). Macroscopic current shows close correlation with microscoping Na+ current. Probability of channel opening depends on membrane potential, increasing as potential is depolarized
What did the cell-attached patch clamp reveal about K+ channels?
Most channels open with a delay, but remain open during depolarization. Probability depends on potential.
How do voltage gated channels work?
Detect voltage, change conformation to open a pore.
How do ligand-gated ion channels work?
Change conformation in response to binding another molecule (usually a neurotransmitter)
What is the role of active transporters?
Generation and maintenance of electrochemical gradients (i.e. Na+/K+ pump).
What are the three types of active transporter?
ATPase Pumps, Ion exchangers (Antiporters and co-transporters)
How do ATPase Pumps work?
Requires ATP as energy source (e.g. Na+/K+ pump)
How do antiporters work?
Use energy of electrochemical gradient. Na+/Ca2+ exchanger moves Ca2+ against gradient based on Na+ gradient. Na+/H+ exchanger helps maintain pH.
How do co-transporters work?
Use energy of electrochemical gradient. Carries multiple ions in the same direction.
What are synapses?
Functional connection b/n neurons (transmission of information b/n presynapse and postsynapse)
What are electrical synapses?
Current flows through connexons (specialized membrane channels that connect 2 cells at gap junctions). Direct communication; physical connection. Allow synchronization.
What are chemical synapses?
Presynapse secretes neurotransmitters that diffuse across synapse (secondary current flow) and bind to post-synaptic receptors. Binding results in changes to membrane potential.
Where are gap junctions found?
Skin, smooth muscle, cardiac muscle, glial cells, etc.
What are gap junctions?
Paired sets of aligned ion pores/connexons; larger than voltage gated pores. Hexameric connexon formed from 6 connexin subunits.
What is the time frame for an action potential with the presynapse and postsynapse relative to each other?
The postsynaptic neuron is depolarized within a fraction of a millisecond.
What are ionotropic receptors?
Ligand-gated ion channels. Neurotransmitter binds and channel opens. They are short acting.
What are metabotropic receptors?
G-protein coupled receptors that do not have an ion channel as part of their structure (requires metabolic change). NTX binds, G-protein is activated, modulate ion channels (signalling cascade) and it opens. They are slow acting.
What is the active zone in a chemical synapse?
Place where synaptic vesicles discharge neurotransmitter into synaptic cleft
What is post-synaptic density?
It is responsible for post-synaptic signalling.
What are small molecule neurotransmitters and how are they formed?
- e.g. ACh, DA, Glu
- Enzymes to synthesize these neurotransmitters produced in cell body
- Slow transport to terminal (in pieces)
- NTX precursors enter from extracellular space
- NTX produced and packaged (small vesicles) in terminal
What are Neuropeptide neurotransmitters?
- Enkephalin
- Enzymes and precursors produced in cell body
- Packaged into large vesicles in soma
- Fast transport to terminal
- Modification in terminal if necessary
What is the process that occurs at chemical synapses?
- Transport of NTX precursers from soma to terminal.
- Synthesis/modification of NTX and packaging into vesicles.
- AP arrives and depolarizes membrane.
- Voltage-gated Ca2+ ion channels open, Ca2+ rushes in. - Ca allows vesicles to fuse with presynaptic membrane.
- NTX released via exocytosis
- NTX binds on postsynaptic membrane and induces ion channels to open/close
- EPSP or IPSPs are generated
- NTX removed by reuptake/glial cells/degradation
- Vesicular membrane recycled via endocytosis
What is calcium’s role at the presynapse?
Influx of calcium triggers NTX secretion, as indicated by change in postsynaptic membrane potential. Blocker eliminates postsynaptic response.
What is synaptic vesicle docking?
Four SNARE proteins responsible for docking/fusion of vesicles and presynaptic membrane.
- SNARE complexes form as vesicle docks.
- Synaptotagmin binds to complex
- Ca2+ binds, curving membrane and bringing them together.
- Fusion = exocytotic release
What are the three SNARE proteins that make the SNARE complex?
Synaptobrevin (vesicle membrane), Syntaxin (presynaptic membrane) and SNAP-25 (presynaptic membrane)
What does synaptotagmin do?
Binds with Ca2+ and changes conformation to connect with other SNARE proteins.
What is the process of vesicular recycling?
Endosome -> Budding -> Docking -> Priming -> Fusion (exocytosis) -> Budding (endocytosis)
- Following addition of synaptic vesicle membrane (exocytosis) clathrin triskelia attach to vesicular membrane
- Polymerization causes membrane to curve/constrict (dome)
- Dynamin forms ring-like coil around lipid stalk connecting vesicle-membrane and pinches off vesicle.
- Uncoating yields recycled vesicle
What receptors are ionotropic?
nACh, AMPA, NMDA, Kainate, GABA, Glycine, Serotonin, Purines
Which receptors are metabotropic?
Muscarine, Glutamate, GABAb, Dopamine, Adrenergic, Histamine, Serotonin, Purines
What are EPSPs?
Increase likelihood of postsynaptic AP (depolarizing)
What are IPSPs?
Decrease the likelihood of a postsynaptic AP (hyperpolarizing)
What is post-synaptic potential summation?
EPSPs and IPSPs summate over time/space to allow subthreshold signals to influence AP production. Integrates responses.
What are the categories of small-molecule neurotransmitters?
Acetylcholine, Amino acids, Biogenic amines
What are the categories of biogenic amines?
Catecholamines, indoleamine, and imidazoleamine
Which amino acids are small-molecule neurotransmitters?
Glutamate, Aspartate, GABA, Glycine
What are the catecholamines?
Dopamine, norepinephrine, epinephrine
What is the indoleamine?
Serotonin
What is the imidazoleamine?
Histamine
Describe acetylcholine
- Excitatory
- Precursors: Choline/acetyl CoA
- Rate-limiting step: ChAT (choline acetyltransferase)
- Removal: AChE (acetylcholinesterase)
- Small, clear vesicle
Describe glutamate
- Excitatory
- Precursor: Glutamine
- Rate-limiting step: Glutaminase
- Removal: Transporters (EAATs)
- Small, clear vesicles (by VGLUTs)
- Most important for brain function
- Does not cross BBB
- Back to glutamine in glial cells
Describe GABA
- Inhibitory
- Precursor: Glutamate
- Rate-limiting step: GAD
(Glutamate -> GABA) - requires co-factor from Vit B6
- Removal: Transporters
- Small, clear vesicles (VIAAT)
- primary inhibitor NTX
Describe the catecholamines
- Excitatory
- Precursor: Tyrosine
- Rate-limiting step: Tyrosine hydroxylase
- Removal: Transporters, MAO, COMT
- Small, dense-core or large, irregular dense-core vesicles
Describe serotonin
- Excitatory
- Precursor: Tryptophan (essential AA)
- Rate-limiting step: Tryptophan hydroxylase
- Removal: Transporters, MAO
- Large, dense-core vesicles
- Synaptic effects terminated by SERT
- Found in Raphe nuclei
Describe the neuropeptides
- Excitatory and Inhibitory
- Precursors: Amino acids (protein synthesis)
- Rate-limiting step: Synthesis/transport
- Removal: Proteases
- Large, dense-core vesicles
Describe the endocannabinoids
- Inhibits inhibition
- Precursors: Membrane lipids
- Rate-limiting step: Enzymatic modification of lipids
- Removal: hydrolysis by FAAH
- No vesicles
What are the receptors for ACh?
- Nicotinic Acetylcholine Receptors (nAChR)
Ligand-gated ion channel. Conformational change in extracellular domain with binding, gate opens - Muscarinic Acetylcholine Receptors (mAChR)
Metabotropic G-protein coupled receptors. Can be either excitatory or inhibitory.
Through which pathways does ACh travel?
Basal forebrain, cholinergic cells, hippocampus.
What are the receptors for glutamate?
AMPA - primary mediators of excitatory transmission - ligand-gated ion channel NMDA - 'coincidence detectors' - allows Ca2+ entry - requires co-agonist glycine - Mg2+ blocks pore with hyperpolarization - ligand-gated ion channel ** Key role in LTP mGluRs - G-protein coupled - Glu binds inside venus flytrap - excitatory or inhibitory
What are the receptors for GABA?
GABAa
- Ionotropic
- Cl- influx with GABA activation (hyperpolarization)
- Depressants enhance GABA
GABAb
- G-protein coupled
- GABA binds in venus flytrap
- Conformational change w/ binding of G proteins
- Can be inhibitory through activating K+ channels or blocking Ca2+ channels
Describe dopamine
- Reinforcement
- synthesized in presynaptic terminal
Tyrosine -> DOPA -> Dopamine - packaged by VMAT
- Reuptake = Na+ dependent DA co-transporter (DAT)
- D-1 Like receptors (D1, D5) are excitatory
- D-2 Like receptors (D2-D4) are inhibitory
- DA receptors activate/inhibit adenylyl cyclase
- Found in Substantia nigra (movement/coordination)
Describe norepinephrine
- From dopamine
- Cleared using NET
- Increased with amphetamines
Descripe epinephrine
- From norepinephrine
- NET can take it up
- regulates cardiac function/respiration
- Found in medullary epinephrine neurons, thalamus, hypothalamus
What happens with norepinephrine/epinephrine bind to receptors?
Inhibits K+ channels
- alpha-beta-adrenergic metabotropic receptors
Serotonin receptors
Most 5-HT receptors are metabotropic, but 5-HT3 receptors are excitatory post-synaptic ligand-gated ion channels
What is plasticity?
A highly dynamic process of neural change resulting from experience
What are the 4 forms of short-term plasticity?
Facilitation, depression, augmentation and potentiation
What is synaptic facilitation?
The rapid increase in synaptic strength that occurs when 2+ APs meet at presynaptic terminal within a few msec of each other. Enhances postsynaptic response. Time-dependent.
What are synaptic augmentation and potentiation?
Increased release of NTXs from the presynaptic terminal via enhanced Ca2+ ability to trigger fusion of vesicles w/ membrane. The main differences are b/n when it occurs and for how long.
What is augmentation?
Follows facilitation. It is transient, occurs over a few seconds, and results in slight potentiation.
What is post-tetanic potentiation?
Over a slow time course (sec to min), potentiation after stimulus is removed. Sharp increase, and prolonged decrease of response.
What is tetanus?
High-frequency train of stimulation
What is synaptic depression?
A short-term decrease in synaptic strength resulting from depletion of synaptic vesicles at synapse. Rapid decrease in NTX release. Rapid recovery when stimulus is removed.
What is the vesicle depletion hypothesis?
The relative rate of synaptic depression is proportional to the rate of neurotransmitter release
What is the role of synapsin?
Maintains vesicles in a reserve pool, which replenishes release pool. When inhibited, rapid rate of depression.
What is habituation?
The process that causes an animal to become less responsive to repeated occurrences of a stimulus
What is sensitization?
The process that allows an animal to generalize an aversive response to a variety of other non-aversive stimuli.
What did the gill withdrawal reflex show in brief vs repeated pairings?
Brief - short-term sensitization w/ shock
Repeated - long-term sensitization
What are the mechanisms underlying the gill withdrawal reflex?
The modulatory/facilitatory interneuron enhances ability of sensory neuron, and restores ability of interneurons and motor neurons to act on the gill using serotonin. Serotonin increases protein synthesis for enzymes
What is the tri-synaptic circuit of the hippocampus?
Dentate gyrus -> CA3 -> CA1
When was LTP seen in the mammalian hippocampus?
With tetanus stimulation. Only works when pre- and postsynaptic terminals are stimulated
What is Hebb’s Postulate?
Neurons that fire together, wire together. Requires a coincidence detector which allows LTP to occur only when both pre and postsynaptic neurons are active.
What is calcium’s role in LTP?
Ca2+ increases probability of LTP. Initiates postsynaptic signalling cascades with CaMKII and PKC.
What does LTP do?
Increases postsynaptic sensitivity to presynaptic signals (structural changes). Sustained LTP is dependent on proteins, so protein inhibition suppresses EPSP
What is the role of CaMKII and PKC in LTP?
CaMKII - Actively involved in structural changes
Both - Increase AMPA receptors (removes NMDA block), and increase ability of membrane to respond to pre-synaptic stimulation
What is early-phase LTP?
Mediated by AMPA receptor trafficking from recycling endosome - typically encompasses first 2 hours of LTP.
What is late-phase LTP?
Mediated by downstream events at genetic level, involving protein synthesis and transcriptional regulation. Responsible for persistent expression of LTP.
What are the key parts of early-phase LTP?
Coincidence detector, Ca2+-mediated protein kinases (CaMKII and PKC), AMPA receptor trafficking, recycling endosomes
What are the key parts of late-phase LTP?
cAMP, PKA, CREB, synaptic growth proteins, transcriptional regulation
Where does long-term depression occur?
Hippocampus and cerebellum
Under what circumstances does LTD occur?
Low frequency stimulation
What is a phosphotase?
Cleaves phosphate groups from proteins, typically resulting in deactivation.
Which two phosphotases are important in LTD?
PP1 and Calcineurin (PP2B)
What is the neural mechanism of receptor deactivation in LTD?
Progressive entry of Ca2+. Slow increase of Ca2+ activates protein phosphotases (PP1 Calcineurin).
How does LTD occur in the cerebellum?
Low Hz paired stimulation of climbing and parallel fibres causes LTD that reduces parallel fiber EPSP.
- NOT ionotropic receptors
- VGCC = voltage gated Ca2+ channels
- gradual time frame
- LTD = slow increase of Ca2+ which activates different proteins
What are some important concepts for cerebellar LTD?
- NMDAR-independent
- Kinase instead of phosphotase
- Voltage-gated Ca Channels
- IP3 Receptors and PKC are coincidence detectors
