Physiololgy, Anatomy and Neurochemistry of Brain Circuits Flashcards

1
Q

What is Behavioral. Neurobioology?

A

Behavioral NeuralBiology- the understanding of the physiology, anatomy and neurochemistry of brain circuits that generate that behavior

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2
Q

Explain the pattern of generation behavior starting from the cell.

A

Pattern:
* Cell-> Network-> Circuit->Behavior
How the cell generates activity and how activity of cells are represented at neuronal network level. The activity at the network is generates throughout a circuit in the brain, whic h will generate behavior.

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3
Q

What is the oldest written piece of evidence of the word brain in the world?

A

First writing of words brain in Hieroglyphics (by Edwin Smith)
-dates back to about 3400 years ago

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4
Q

Discuss the brief history of neuroscience including the importance of Santiago Cajal and Camilio Golgi. What was the Neuron Doctrine and what did it entail?

A

Santiago Cajal - neuroscientist who used Golgi stain(invented in 1873) to stain only a small percent of neurons, which allowed Cajal and Golgi to begin documenting somas and processes of a neuron
-1890-1910, the strain of neuron and drawing provided evidence for Neuron Doctrine
-Neuron Doctrine- there are neural units that are specialized and there are nerve fibers called cell processes and a synapse that connects these neurons (opposed to reticular theory: protoplasmic system tubes and pumps moves arms and legs)
Cajal and Camilio Golgi won the Nobel Prize together in 1906 with the concept of CNS (central nervous system) being made of discrete units

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5
Q

Who is Lord Adrian and what discoveries did he make ? Who is Scherrinton and why was he important?

A

Lord Adrian- Electrophysiologist who studied the activity of individual neurons
He observed the idea of activating neurons and when some threshold was hit the neuron would respond with maximal amplitude potential and it would be same amplitude every time
- *All or None Law of Neuronal siganaling : either the cell was not firing or was firing action potentials
-Due to his electrical methods of studying nerve and Brain activity He won the Nobel Prize, 1932

Scherrington: 1890’s- 1920’s introduced the concept of the “Synapse” (important development that ended reticular theory debate)
he won the Nobel prize with Adrian 1932)
Had the idea of REFLEX ARC - reciprocal innervation of opposing muscle groups; idea that you needed excitatory and inhibitory input to activate opposing muscle
“idea that muscles are governed by excitatory and inhibitory impulses “
-he thought about “enchanting loom (strings and fibers) in brain; millions of flashings shuttles weaving a pattern” (how he envisioned brain working)

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6
Q

What are reflexes? Where do they occurr in the body?

A

Reflexes:
-fast, stereotypical, inborn, protective actions
-Occur at spinal cord or brainstem levels
-May be monosynaptic or polysynaptic

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7
Q

What are the requirements for reflexes? Discuss the example Patellar reflex and mechanism behind it.

A

All reflexes require:
-Stimulus at receptor
-Sensory information relay
-processing at CNS level
-activation of motor response
-response of peripheral effector
ex:
Patellar reflex: physician taps the patella ( knee bone) and you have stretch of quadriceps muscle. The stretch receptors in the quadriceps muscle sends an excitatory signal into spinal cord. some fibers form neurons activate alpha motor neurons in same muscle, causing quads to contract. At the same time, alpha motor neurons will activate inhibitory neuron to shut off opposing alpha motor neuron and relax opposing muscle for response (foot jerk up to patella tap)

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8
Q

Discuss the history behind the neurotransmitter, including scientists that were a part of its discovery. Explain who Sir Henry Dale, Otto Loewi, and Sir John Eccles were and their achievements

A

The neurotransmitter (chemical communication at a synapse)
-Sir Henry Dale: first Identified Acetycholine as a possible neurotransmitter in PNS (won Nobel Prize with Loewi in 1936)
“Dale’s Principle”- one neuron, one transmitter (thought neurons can be differentiated by transmitter release; ex GABA, ACh)
Dale and Loewi- pals who discussed whether the synaptic connections transmitted information across another, either chemical or electrical transmission

-Otto Loewi: 1921, “Vagusstuff experiment ( studied frog hearts and stimulated the vagus nerve which slowed heart in frog)
-theorized something came from vagus nerve that had to slow down heart . The stuff had to be chemical.
This experiment helped prove that synapses use chemical transmission to help communicate with neurons.
-won Nobel Prize with Dale in 1936.

-Sir John Eccles : Favored Electrical synaptic transmission in CNS
-He was a student of Scherrington
Did a series of experiments that proved synapse was an electrical connection (try and prove Dale and Loewi wrong)
-1951, critical experiment that confirmed Chemical transmission in CNS (and PNS)
(won Nobel Prize with Hodgkin iand Huxley, 1963)

Later found that there are specific proteins in synapse that form electrical conduits , so Eccles, Dale and Loewi were all right, since a synapse uses both chemical and electrical neural transmission

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9
Q

Discuss the scientists who discovered the action potential

A

The Action Potential
- Alan Hodgkin and Andrew Huxley (1952)
-they used squid giant axon that they stuck an electrode inside axon, and found interior is negative; When action potential occurs, it becomes very positive. After AP, it drops below original voltage and then recovers which corresponds to wave of activity of voltage moving down axon
-*Came up with Mathematical model that describes how action potentials in neurons are initiated and propagated
(Nobel Prize with Eccles 1963)

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10
Q

Who were the scientists that studied Neural coding and activity in different brain areas ? Motor and visual cortex? Anesthesized animals? Cerebellum?

A

Neural Coding (1950s)
Vernon Mountcastle- studied motor cortex in anesthetized monkeys (to understand when neurons fire in neuromotor cortex, how it generates movement and behavior.
-D Hubel and T Wiesel- studied Visual cortex, anesthesitized cats and monkeys( to figure how neurons represent visual stimuli around you)
-Ed Evarts- Motor cortex, awake monkeys
-Eccles, Ito, Szentagothai- Cerebellum (to understand how neurons do their magic)
-Thach and Llinas- Cerebellum

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11
Q

Discuss the electrophysiological Techniques that occurred in neuroscience and the scientists that came up with these ideas

A

Electrophysiological Techniques:
-Luigi Galvani (1737-1798) “animal electricity” :
-considered the Founder of of Electrophysiology;
Found that animal electricity generated muscle movement and behavior
Used frog body (Lower half) and exposed wires in experiment
Experiment (insert wire through vertebral canal in frog and touch body with lancet, causing legs to contract and sparks from electrical machine)
-EEG(electroencephalograph) - 1924, Hans Berger (from his son) wired up his son and recorded electrical activity in brain
“Brain generated constant activity”
-Field Potentials (localized recording, like Berger)
-Intracellular Recording (within brain )
1931, squid giant axon
-Intracellular Recording
1951, CNS neurons
-Extracellular Recording
-1950s
-Microiontophoresis (allowed us to deliver known quantities of transmitters or drugs onto neurons)
1967
-Patch Clamp (allows people to understand the current of individual channels or small groups)
1980s
-Optogenetics (manipulate neuronal activity with light being shone)

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12
Q

Describe what happens when an action potential is propagated. How does frequeny of spikes change with action potential?

A

Action potential:
-Influx of Na+
-Outflux of K+
-An action potential is a self-regenerating electrical pulse traveling along the axon (either unmyelinated or when hopping to node to. node of Ranvier when myelinated)

*The greater the action potential, the more spikes arre generated (> frequency of spikes are generated)

Process: initial segment at Node of Ranvier- large density of Na+ and K+ channels
when voltage reaches threshold (by concentration of Channels), Na+ channels open up and Na+ ions rush in, which drives membrane voltage into positive region. positive voltage drives K+ channel to open which causes K+ ions to rush outside cell and bring back membrane potential below initial membrane potential which then recovers

inside of a cell has a membrane potential of -68 mV
glutamate binds to receptor or GABA binds to receptor, they will generate excitatory post-synaptic potentials or inhibitory post-synaptic potentials( raise the voltage inside the cell or decrease the voltage)

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13
Q

What is the function of Patch Clamp Recording and how does it work?

A

Patch Clamp Recording - study the activity of Channels or receptors
- used to study Synaptic Inputs- EPSPs/IPSPs
-Drug responses (study responses of channels to drugs)
process: remove mouse brain, cut into slices and dissociate neurons of a slice. Then take a glass pipette (heat glass) and move it to edge of cell, where glass sticks to lipid membrane. Give suction to create seal between lipid and glass
Now do Cell-attached recording: allows you to record currents going across patch of membrane or inside cell)
can do whole cell recording, outside-out patch and inside out patch

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14
Q

What occurs in Intracellular Recording and why is it important

A

Intracellular Recording - Interrogate how the ENTIRE cell is processing information
- Active and passive membrane properties (channels, resistance capacitance)
-Excitability
-Channel properties
-Transmitter responses

Slice up brain, put it in chamber with artificial cerebrospinal fluid and sugar sucrose and O2 to keep it alive. Large electrode to puncture cell, and read voltage inside cell; inject electricity current into the cell. The way membrane responds below threshold helps you understand how excitable neurons are and how easily neurons discharge and drugs that affect it. Can increase electrical impulses and generate APs.

stimulate microeletrode to inject current
-record microelectromechanical to measure membrane potential

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15
Q

What is Extracellular Recording and how does it work ?

A

Extracellular Recording: Record activity of a single neuron or many neurons at once
Ex: take a platinum tungsten electrode that is covered in quartz glass (or resistive compound) and stick the electrode in brain cell to listen to action potentials.

Different types of electrodes
-Generate things that look like daggers with individual pad to record many cells at once in linear form
- bed of nails: hundreds of electrodes sticking up, take wafer and flip over and insert into brain to record neurons in plane form (ex :neurons encode information)
-tetrode form- record neurons from multiple pads or electrodes to , differentiate who is firing Action potential

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16
Q

What is Spike sorting/classification and why is it important in neuroscience?

A

Spike sorting/classification: Computational method of DISCRIMINATING extracellular activity from different neurons
used to figure out which cell is firing amongst many cells around
use unique features of AP (shape) to separate them out.

17
Q

What occurs in Multichannel recording?

A

Multichannel recording- Monitor many neurons, simultaneously
-get an idea of how large populations encode a cognitive function, behavior or sensory phenomenon
-record hundreds, thousands of cells on dot roster.
every time, fire action potential, put a dot on page

18
Q

What are the advantages of Multi-Neuron Recording?

A

Advantages; Multi-neuron recording
-Monitor many neurons, simultaneously
-Awake animals- full spectrum of behavior
-test variety of stimulus conditions or drug doses
-Multiple hypothesis testing- Data mining
-Evaluate cellular, circuit and network functions, simultaneously
-Long term studies
-Examine Physiologic effects or drug actions at multiple sites along a pathway (simultaneous electrophysiology and neuropharmacology)
-Bridge the “gap” between cells and behavior

19
Q

what is rate encoding?

A

Rate encoding- way of measuring the number of spikes (or frequency of action potentials) based on stimulus for a set period of time
The neuron has to communicate to cell how strong the stimulus was for that neuron
(done so by firing more action potentials )
- the stronger the stimulus, the greater frequency of action potential

at beginning of AP, there is a burst pattern that happens and encodes velocity, but describes the onset of pressure
as input gets greater you reach threshold and fire more action potentials from neuron

20
Q

How do you represent things that sinlgle neurons can’t?
review (slide 20)

A

-As information ascends from the skin or retina into the cortex, a single neuron can synapse on many other neurons at another neuron
**you can AMPLIFY a signal multiple times to get a larger dynamic range than from single neuron alone”
as neuron is more stimulated, more peripheral neurons are activated- receptive field
encode:
*recruit more neurons as information is sent to Cortex

21
Q

what is the receptive field and what role does it play?

A

Receptive Field: a specific region in sensory space, where an appropriate stimulus can drive an electrical response in sensory neuron
-Size of receptive field determines sensitivity to stimulus
-Ability to differentiate stimuli locations or modalities (e
-2-point discrimination
-color
-Auditory frequency
understanding who was firing, allow you to knolw where on skin, firing happened
more neurons you get firing, the more recruiting of neurons and receptive field gets more overlap (harder to determine where you are)

22
Q

What air some good receptive field examples ?

A

1.Somatosensory experiment (directional)
non-human primate’s hand and six directional points with each of letter that corresponds to action potential train,
ex: letters W-F: stroking hand from fingertips to wrist
-cell has a particular preference (only fire when touch a series of dermtones in particular order :
-uses receptive fields with directional sensitivity

  1. Working memory task of non-human primate
    Have a Visual screen and in center is fixation point. Animal asked to stare at center of screen fixation point.. in animal’s visual field, a cue shown screen briefly.
    The rat or monkey must remember where that occurred in space and when focal point goes away, the animals can make a response to look at where cue was
    working memory task- must keep information of where cue was to know where to move.
    - neuron fires briefly when cue is there
    when animals remembering where cue was, firing is more frequent
    if cue is down in south west corner, no cue
23
Q

What is EEG? How does it work ?

A

EEG (electroencephalogram)- a form of electrophysiology
-an array of electrodes on a 10/20 system
take distance between two areas, 10% and 20% when laying electrodes to cover skull and record electrical activity
**electrodes record Scalp voltages that are an echo of underlying neuronal activity **
when thalamic neuron is firing or spiking, it begins alpha waves (neurons firing and oscillatory activity of EEG have direct relationship )

in cortex, pyramidal neurons are organized in column
when column discharges, it creates parallel electromagnetic field that generates oscillatory electrical currents and potentials recorded in EEG
(changes in activity in hippocampus can affect activity in thalamus )

24
Q

What are the many uses of EEG?

A

Clinical EEG used for:
Detecting Seizures
-Sleep (look at sleep/wake architectures or sleep dysfunction)
-ADHD (attention deficit hyperactive disorder)
Concussion

ex: EEG used to detect disease state like ADHD (changes in beta and theta and drugs used to treat the disease can reverse oscillitary deviances)
use EEG to observe and predict seizure activity and try and stop it (by injecting current into brain)
(different frequencies, power or loudness of frequencies on graph)

25
Q

What is Neuroanatomy? Discuss the structural and functional components of an MRI

A

Neuroanatomy- the study of anatomy and the organization of the Nervous system
used to identify different regions of the brain; provide some mapping
-Gross Anatomy- dissections
-MRI (magnetic resonance imaging): way of looking at how magnets align and flip proton spins (look at compounds in brain)
-Structural: Imaging Gray and White Matter
-DTI: Tracing White Matter Connections ( Diffusion tensor imaging: can trace where nerves are going, or how water moves through white matter tracks in the brain)
-Functional: Tissue activity- O2 saturation of Heme
-The O2 saturation of Heme is a good determinant of how active a particular tissue is.
Bold signal (O2-saturation dependent magnetism of Hb

26
Q

What kind of techniques are used in Neuroanatomy for Non-humans?

A

Neuroanatomy- non-human
Retrograde transport of florescent markers.
-(1780s-190s) use florescent dye placed in latex beads
the beads taken up by neurons and transported back to soma
-these methods are only monosynaptic (put dye in cortex and ask what neurons project, or what is density of neurons)
can infect neuron with different neurons carrying florescent marker
label neuron types with in a pathway (understand where particular neuron type goes)
use viruses (Rabies (pro) or Herpes Simple’s virus) that jump synapse and do multi-synaptic labeling

27
Q

Discuss the structural and functional components of Clarity technique

A

Neuroanatomy; Clarity (very powerful)
a way of understanding how neurons are connected to many other neurons , making brain tissue transparent
-Clarity technique: take a tissue from brain , embed in hydro gel and use electrophoresis to remove things from brain and clear the brain. Once brain is clear, you add antibodies to tag particular things of interest (ex; NE neurons, Glutamate neurons) and get highly detailed image of proteins, nucleic acids or organs

used to see where fibers are, better understanding at how different neurotransmitter systems interact on micro and macro scale

28
Q

List the timeline for Neurotransmitters and discoveries that were made

A

Timeline for Neurotransmitters
1890-1910 concept of Synapse
1919-1950: Acetylcholine (slow heart down) and Norpepinephrine (speed heart up) identified as PNS transmitters with associated pharmacology
-1950-1975: Catecholamines, serotonin, acetylcholine, GABA identified as CNS transmitters GABA-. inhibitory; Glutamate-> inhibitory) , mechanisms of release and degradation identified, second messengers
1975-1990: Amino acids, peptides, receptors
-1990- present : Receptorology(driven by molecular biological techniques) ,, nitric oxide, trophic factors

Nitric Oxide- retrograde transmitter; help with learning and memory.
THE post-synaptic neuron generates signal that is used for pre-synaptic signal to do its actions.

29
Q

List the Neurochemical Techniques that were discovered

A

Neurochemical techniques:
-Histochemical and Immunostaining
-Microdialysis
-In Vivo Voltammetry
-Chronoamperometry
-Fast Scan cyclical voltammetry
-Redox Cycling
Chemogenetics- DREADDS
-(Designer Receptor Exclusively Activated by Designer Drugs)

30
Q

What kind of techniques are used for finding the chemical identity of neurons ?

A

Chemical Identity of Neurons:
-Immunohistochemistry
-In situ hybridization
these techniques are used to identify where neurons are located, how they interact with other neurons, and what circuits are they in,
combining the two techniques we can understand how dopamine and glutamate interacts and where myelin based proteins are

myelinated fibers(blue) are tagged, target mRNAs (yellow)

31
Q

what is Microdialysis and how does it work?

A

Microdialysis- allows us to sample extracellular neurotransmitters when they are released
-technique used to understand how different tonic levels of neurotransmitters generate state-dependent behavior (feedings, sleeping wake, stress)

Process:
like kidney dialysis- piece of dialysis memories, cartridges that strands mice across, build container around it, push artificial cerebrospinal fluid in membrane and another tube take things diffused across membrane and collect in vial, analyze on mass spectrometry, or UV detection

32
Q

what is In Vivo Electrochemistry used for and how does it work?

A

In Vivo Electrochemistry: used for the OXIDATION/REDUCTION of small molecules
- it was developed by Wightman and colleagues wrote a series of novels explaining the technique
Process:
piece of carbon fiber wrapped in glass and stuffed in the brain to measure the instantaneous changes in n neurotransmitters like dopamine, NE, serotonin. Yo do that by changing the voltage (raise and lower it).
ex: In dopamine, when you change voltage, you lose H and create compound called quinone. The current generated from redox reaction will be recorded

33
Q

what is Microiontophoresis?

A

Microiontophoresis- allows us apply drugs or neurotransmitters at relatively localized area-technique used to understand how two neurotransmitters interact and affect neuronal activity (ejecting molecules of drug by applying change to electrode)
Process
-Multibarrel pippette- grouping of glass tubes come together at single point; allows you to load salt solution in one barrel and other drugs to other barrels
you can push out molecules of drug by creating charge In electrode
ex Purjinke neuron spontaneously firing, every time GABA is ejected into cell, it shuts off; if add NE, the suppression of activity Is bigger (NE- modulator of glutamate ) take of NE, goes back to baseline conditions
-

34
Q

Explain what the Cumulative Raster Record and Peri-event Histogram is used for

A

Cumulative Raster Record and Peri-event Histogram
-Set of experiments done to
- Visual neuron: when you go from right to left or left to right, the neurons fires
-when add NE: response is sharper
when take off NE: goes back to baseline conditions
-you can tune how sensitive your neuronal network is to a spatial location on dermatomes or visual field.
-in another experiment, there is a neuron that is not firing. But when you add NE; neruon will start firing
to movement of light across visual field
-hence you can make a neuronal system more sensitive than what it would normally be by adding neuromodulator to it

-wh

35
Q

What is Optogenetics and how does it work?

A

Optogenetics: new technique used to SELECTIVELY activate transmitter specific pathways
- will manipulate neurons and circuits
use viral vector to introduce a gene into a neuron
ex: AVV virus that comes from cladimonis Rhihardi (green algae)
-take this protein that responds to light and opens channel and allows sodium to fly in.
ex; shine blue light into rat’s brain. in neural fibers thy express rhodopsin and activate added
-activate or inactivate neuronal channels using different types of channel or halo Rhodopsin
chemogentics- DREADDs designer receptor activated by Designer drug
receptor only bind to designer drug, in order to specifically activate certain pathways.

36
Q

List the emergent technologies that are being developed in neuroscience

A

Emerging technologies:
-Walking animal preparations– physiological conditions
-Specific behavioral tasks- modeling of executive functions
-Many-neruon recording –within and across brain regions
-Electrical microstimulation: activation of intrinsic pathway
-Optogenertic stimulation: Phasic stim transmitter pathways
-Chemogenetic stimulation– tonic stim transmitter pathways
-Neurochemistry– detect transmitter levels
-Long term recording- longitudinal studies
-Viral tract tracing—> dissection of neural circuits