Term
| what is the "instructive signal for learning"? |
|
Definition
|
|
Term
| what does dopamine affect in ADHD? |
|
Definition
|
|
Term
| what does dopamine affect in Parkinson's Disease? |
|
Definition
|
|
Term
| depression results from disruption of the ______ system |
|
Definition
|
|
Term
| how is dopamine changed in schizophrenia? |
|
Definition
|
|
Term
| OCD is a disorder associated with dysfunction of the ______ system |
|
Definition
|
|
Term
| number one mechanism of addiction is that it hijacks the ______ system |
|
Definition
|
|
Term
| Tourette's Syndrome ticks result from issues with ______ |
|
Definition
|
|
Term
| what neurotransmitter has cell bodies that express tyrosine hydroxylase (TH)? |
|
Definition
|
|
Term
|
Definition
| tyrosine --> (via tyrosine hydroxylase) --> L-Dopa --> (via aromatic L-amino acid decarboxylase (AAD)) --> dopamine |
|
|
Term
| 2 places dopamine is found |
|
Definition
|
|
Term
| do many neurons synthesize dopamine? |
|
Definition
| no! (but it does a ton of things in the brain) |
|
|
Term
| 2 dopamine pathways in the brain |
|
Definition
1. mesocorticolimbic
2. nigrostriatal |
|
|
Term
| VTA = ______ dopamine neurons projections |
|
Definition
|
|
Term
| SNc = ______ associated dopamine neurons projections |
|
Definition
|
|
Term
| what determines how dopamine is going to affect the cell? |
|
Definition
| the type of receptor that the neuron expresses! |
|
|
Term
| difference between D1 & D2 metabotropic dopamine receptors |
|
Definition
D1: Gs-coupled receptors
D2: Gi-coupled receptors |
|
|
Term
| D1 type dopamine receptors ______ activity of target cells |
|
Definition
|
|
Term
| D2 type dopamine receptors ______ activity of a neuron |
|
Definition
|
|
Term
| is it possible for some cells to express both kinds of dopamine receptors? |
|
Definition
|
|
Term
|
Definition
| means that they don't themselves open & allow ions to flow across the membrane but instead are coupled to intracellular signaling cascades |
|
|
Term
| GPCRs (G-protein coupled receptors) are examples of _____ receptors |
|
Definition
|
|
Term
| GPCRs have ______ transmembrane domains |
|
Definition
|
|
Term
| 3 subunits in trimeric G-proteins |
|
Definition
|
|
Term
| largest & most diverse group of receptors in eukaryotes |
|
Definition
|
|
Term
|
Definition
| inform the cell about its environment |
|
|
Term
| what is the evolutionarily conserved process by which extracellular signals are converted to intracellular signals for the cell once a GPCR is activated? |
|
Definition
| upon activation, alpha subunit converts uses GTP & dissociates from receptor --> alpha & gamma subunit go to their thing (can be separate!) |
|
|
Term
| one of the ultimate target molecules of G-alpha signaling |
|
Definition
|
|
Term
| one of the ultimate target molecules of G-beta/gamma signaling |
|
Definition
|
|
Term
| can different parts of G-protein have different functions within the cell? |
|
Definition
|
|
Term
| why do about 1/3-1/2 of all marketed drugs target some type of GPCR? |
|
Definition
| they can greatly amplify/prolong an extracellular signal in an intracellular cascade |
|
|
Term
| 3 main types of G-alpha subunits (very important to whether a GPCR will increase or decrease neural activity) |
|
Definition
1. G-alpha-S (Gs)
2. G-alpha-i (Gi)
3. G-alpha-q (Gq) |
|
|
Term
|
Definition
| an enzyme that sits in the lipid bilayer; its job = make cAMP |
|
|
Term
|
Definition
| an enzyme that sits in the membrane; when activated, increases activity of small molecules (ex. IP3, DAG) |
|
|
Term
| D1 type dopamine receptors coupled to Gs proteins --> _____ when binds to dopamine |
|
Definition
|
|
Term
| D2 type dopamine receptors coupled to Gi proteins --> decrease cAMP activity when binds to dopamine --> ______ neural activity |
|
Definition
|
|
Term
| why can dopamine be involved in so many functions in the brain? |
|
Definition
| there are various pathways & within a pathway various kinds of receptors for dopamine |
|
|
Term
| ______ is central to the formation of operant memories |
|
Definition
|
|
Term
| is the dopamine signal rewarding or aversive? |
|
Definition
|
|
Term
| how do you demonstrate that dopamine is necessary & sufficient for learning the operant task? |
|
Definition
"necessary" test: no dopamine --> no learning
"sufficient" test: all you need is dopamine --> learning |
|
|
Term
| initial phase of monkey/juice reward experiment |
|
Definition
| monkey sits in chair & stares at screen --> when it sees a rewarded symbol he licks a spout to get a juice reward --> record from neurons in the VTA (extracellular recordings so you see on the read-out little tick marks when APs from dopamine neurons happen) --> there are a lot more spikes right after the monkey gets the juice reward |
|
|
Term
| graph showing tick marks when APs happen within a neuron across various trials |
|
Definition
|
|
Term
| sum of the APs at a certain time point on a Raster plot |
|
Definition
| Peristimulus Time Histogram (PSTH) |
|
|
Term
| second phase of monkey/juice reward experiment |
|
Definition
| dopamine bursts when first juice is delivered --> monkey will start paying attention to what happens just before they get the juice --> dopamine will increase when it learns that purple star means juice is coming --> a lot of learning, dopamine will increase at star & not juice! |
|
|
Term
|
Definition
x axis = time
y axis = trial
marks demonstrate neuron spikes |
|
|
Term
| classic Raster Plot example |
|
Definition
| monkey learning that purple star cue indicates a later juice reward delivery |
|
|
Term
| phasic burst (or phasic firing) of dopamine neurons |
|
Definition
|
|
Term
| tonic firing of dopamine neurons |
|
Definition
| regular (baseline) firing rates |
|
|
Term
| 2 places VTA dopamine neurons target |
|
Definition
1. NAc
2. prefrontal cortex |
|
|
Term
| what does each row in a Raster plot represent? |
|
Definition
|
|
Term
| when does phasic dopamine neuron firing occur in first few presentations of juice reward US? |
|
Definition
| with the unexpected juice reward --> monkey starts paying attention to things that may cue the reward |
|
|
Term
| when does phasic dopamine neuron firing occur after many trials where purple star is a CS for the juice? |
|
Definition
| phasic firing of dopamine neurons gets transferred from the juice to the star |
|
|
Term
| what happens to dopamine neuron firing if the monkey sees the purple star but no juice is given? |
|
Definition
| there will be a pause in dopamine neuron firing |
|
|
Term
| the difference between what reward you were expecting & what reward you experienced |
|
Definition
| reward prediction error (encoded by dopamine neurons) |
|
|
Term
| VTA projects dopaminergic neurons --> ? |
|
Definition
|
|
Term
| SNc projects dopaminergic neurons --> ? |
|
Definition
|
|
Term
| how does potentiation happen in the NAc? |
|
Definition
| recording from a NAc neuron that has AMPARs --> stimulate prefrontal cortex that synapses onto it at the same time as dopamine neuron from VTA is synapsing onto that neuron --> those synapses will be potentiated (as opposed to separate synapses that are associated with other actions) |
|
|
Term
| how does a surprise reward affect dopamine response? |
|
Definition
|
|
Term
| how does dopamine firing look with a completely expected reward? |
|
Definition
| dopamine burst at cue that makes you expect reward but not when reward is given |
|
|
Term
| formula for reward prediction error |
|
Definition
| reward prediction error = actual reward - predicted reward |
|
|
Term
| error signals encoded by the dopamine signal is what drives _______ |
|
Definition
|
|
Term
| what disease can be thought of as essentially extreme reward learning? |
|
Definition
|
|
Term
| what does the "compulsive" nature of addiction mean? |
|
Definition
| you can't stop even though you know it's bad |
|
|
Term
| 2 dissociable aspects of addictive process |
|
Definition
1. learn cues & contexts that predict the availability of drugs
2. once learned, cues motivate drug seeking |
|
|
Term
| large loops across brain area get affected in addiction --> this information eventually gets consolidated into the _______ ("habit center") |
|
Definition
|
|
Term
| the center of the limbic system & addiction circuitry |
|
Definition
|
|
Term
| links rewards to actions/contexts/objects via its various inputs |
|
Definition
|
|
Term
| provides motivation behind actions & ascribes rewards to certain behaviors |
|
Definition
|
|
Term
| drugs of abuse = increase particularly the _______ firing of dopamine neurons |
|
Definition
|
|
Term
| how do actions get manipulated in addiction? |
|
Definition
| teaches the brain which actions were present at the time that the rewarding event occurred & will encourage the brain to seek out those actions in the future |
|
|
Term
| _______ provides a teaching signal that teaches you which actions to do to get a reward |
|
Definition
|
|
Term
| mechanism by which cocaine increases dopamine |
|
Definition
| increase release of dopamine from terminals (VTA --> NAc synapse); increase concentration of dopamine in synaptic cleft |
|
|
Term
| mechanism by which methamphetamines increase dopamine |
|
Definition
| increase release of dopamine from terminals (VTA --> NAc synapse); increase concentration of dopamine in synaptic cleft |
|
|
Term
| mechanism by which nicotine increases dopamine |
|
Definition
| activates nicotinic ACh receptors on VTA dopamine neurons --> increase firing rate of dopamine neurons --> increase the amount of dopamine being released |
|
|
Term
| mechanism by which opioids increase dopamine |
|
Definition
| activate Gi-coupled receptors (especially mu-opioid receptors) on GABAergic interneurons --> decrease activity of inhibitory interneurons in VTA --> disinhibit VTA dopamine neurons |
|
|
Term
|
Definition
| dopamine transporter (DAT) |
|
|
Term
| methamphetamine affect on DAT & VMAT |
|
Definition
reverses DAT
inhibits VMAT |
|
|
Term
| what protein is involved in packaging dopamine into vesicles |
|
Definition
|
|
Term
| dopamine neurons in the VTA get ______ inputs that provide information about context when they should spike |
|
Definition
|
|
Term
| conclusion from Ungless paper |
|
Definition
| a single exposure to cocaine (when paired with glutamatergic input activity) drives LTP at the glutamatergic synapse on dopamine neurons via the learning mechanisms we discussed previously (NMDAR --> calcium --> insertion of more AMPARs) |
|
|
Term
| Ungless figure 1: after cocaine exposure --> _______ in AMPA-mediated currents at VTA synapses |
|
Definition
|
|
Term
| Ungless figure 5: occlusion experiment - did LTP happen in vivo? |
|
Definition
can induce significantly more LTP in saline animals than cocaine
can induce significantly more LTD in cocaine animals than saline |
|
|
Term
| does LTD happen pre- or post-synaptically? |
|
Definition
|
|
Term
| how does LTD help learning? |
|
Definition
| some parts of the brain "learn" by eliminating synapses! |
|
|
Term
| the process by which synapses are removed (often during development) that are not required for efficient information transfer |
|
Definition
|
|
Term
| a particular form of LTD that occurs in the cerebellum |
|
Definition
|
|
Term
| brain area that mediates motor learning |
|
Definition
|
|
Term
| how is the cerebellum different from the cortex/hippocampus in how it operates on learning rules? |
|
Definition
cortex/hippocampus = learning by gaining synapses
cerebellum = learning by eliminating synapses |
|
|
Term
| cerebellum provides _______ adaptive control of movement |
|
Definition
|
|
Term
|
Definition
| Purkinje cells (extremely complex dendritic branching from cell body) |
|
|
Term
| Purkinje cell dendrites = source of input from ______ |
|
Definition
| parallel fibers of granule cells |
|
|
Term
| does a single Purkinje cell have a lot or a few synapses? |
|
Definition
| millions of different synapses & can integrate information about many different aspects from the sensory world |
|
|
Term
| can Purkinje cells self-generate action potentials? |
|
Definition
|
|
Term
| parallel fibers = what kind of neuron? |
|
Definition
| glutamatergic --> glutamate onto Purkinje AMPARs & mGluR1 (metabotropic glutamate receptor) |
|
|
Term
| climbing fibers from inferior olive in brainstem --> input to ______ |
|
Definition
|
|
Term
| anatomical compartmentalization for synapses |
|
Definition
|
|
Term
| how do spine synapses in cerebellum respond to error signal? |
|
Definition
| when error signal arrives, the neuron weakens spine synapses that were active during the depolarization from the climbing fiber |
|
|
Term
| spaces between the spines where there is no glutamatergic input for Purkinje cells |
|
Definition
|
|
Term
| climbing fibers synapse all over the shaft --> make entire Purkinje cell super _______ |
|
Definition
|
|
Term
| climbing fibers activate ______ |
|
Definition
| voltage-gated calcium channels --> influx of calcium --> plasticity |
|
|
Term
| if you just stimulate parallel fibers --> what affect on Purkinje? |
|
Definition
| activates the AMPARs in the spine |
|
|
Term
| can you get plasticity by just stimulating parallel fibers onto Purkinje? |
|
Definition
|
|
Term
| coincident activation between parallel & climbing fibers onto Purkinje |
|
Definition
| calcium comes in when glutamate is being released by parallel fibers --> removal of those specific AMPARs |
|
|
Term
| do climbing fiber synapses change on Purkinje? |
|
Definition
|
|
Term
| presynaptic terminal of parallel fiber --> what kind of input onto Purkinje? |
|
Definition
| glutamate release onto AMPARs & mGluR1 in spine |
|
|
Term
| climbing fiber input onto Purkinje --> what comes into the neuron? |
|
Definition
| calcium coming in (kind of in between spine & shaft) |
|
|
Term
| what affect does PKC have on cerebellar AMPARs? |
|
Definition
| PKC phosphorylates AMPARs --> internalized --> LTD at that synapse |
|
|
Term
| 2 things that need to happen for PKC to be activated in Purkinje |
|
Definition
1. mGluR1 are activated
2. a big calcium signal from climbing fiber input |
|
|
Term
| 9 steps in cerebellar LTD |
|
Definition
1. parallel fiber glutamate
2. binds to mGluR1
3. Gq subunit released intracellularly (is activated)
4. activates phospholipase C
5. phospholipase C cleaves PIP2 into DAG & IP3
6. IP3 increases intracellular calcium
7. activation of PKC (AS LONG AS voltage-gated calcium from climbing fiber is also present
8. phosphorylates AMPARs
9. AMPARs are interalized |
|
|
Term
| symptoms of Parkinson's Disease |
|
Definition
| slowed movement, rigidity, tremor (specifically resting tremor), shuffling gate, stooped posture, blank expression |
|
|
Term
| second most common neurodegenerative disease (behind Alzheimer's) |
|
Definition
|
|
Term
| why is Parkinson's Disease characterized as a movement disorder? |
|
Definition
| main symptom: bradykinesia (slowed movements) or trouble initiating movements |
|
|
Term
| does Parkinson's Disease have cognitive symptoms? |
|
Definition
| yes! despite being known as a mood disorder |
|
|
Term
| does Parkinson's Disease have autonomic symptom problems? |
|
Definition
|
|
Term
| Parkinson's Disease is a disorder of the _______ system |
|
Definition
|
|
Term
| what can you see in control brains that you can't see in PD brains? |
|
Definition
| a black pigment at the SNc (produced by the dopaminergic neurons here) |
|
|
Term
| striatum = input nucleus of ______ |
|
Definition
|
|
Term
| SNc = home of dopamine neurons that project to the ________ |
|
Definition
|
|
Term
|
Definition
1. SNr (substantia nigra reticulata)
2. GPi (globus pallidus internal segment) |
|
|
Term
| BG affects movement by regulating _______ |
|
Definition
|
|
Term
| what does the striatum do when the cortex feeds it with all possible motor commands? |
|
Definition
| filters out motor commands that should be done & motor commands that shouldn't be done |
|
|
Term
| two types of striatal neurons (called "medium spiny neurons" or MSNs) |
|
Definition
1. direct pathway: D1-receptor expressing GABAergic neurons
2. indirect pathway: D2-receptor expressing GABAergic neurons |
|
|
Term
| increase in activity of direct pathway D1 MSNs --> ? |
|
Definition
| decrease activity of output nuclei --> disinhibition of thalamus --> movement |
|
|
Term
| how does indirect pathway affect motor control? |
|
Definition
| suppresses motor commands that you do not want to do |
|
|
Term
| increase of D2 activity --> ? |
|
Definition
| increase in basal ganglia output --> decreases movement |
|
|
Term
|
Definition
| overactive indirect pathway activity --> "break" on movement is too hard |
|
|
Term
| cause of Parkinson's Disease |
|
Definition
| death of SNc dopamine neurons |
|
|
Term
| direct = D1 MSNs --> what effect on movement? |
|
Definition
| inhibitory onto SNr/GPi --> disinhibition of thalamocortical loop --> facilitates movement |
|
|
Term
| indirect = D2 MSNs --> what effect on movement? |
|
Definition
| inhibitory onto GPe --> disinhibition of STN --> excitatory onto SNr/GPi --> inhibition of thalamocortical loop --> suppresses movement |
|
|
Term
| two classes of GABAergic neurons in striatum |
|
Definition
1. D1-receptor-expressing MSNs
2. D2-receptor-expressing MSNs |
|
|
Term
| what kind of receptors are D1 & D2 in striatum? |
|
Definition
| metabotropic receptors coupled to G proteins in the cell |
|
|
Term
| under normal conditions, striatum is bathed in dopamine from ______ |
|
Definition
|
|
Term
| D1 is coupled to ______ G proteins |
|
Definition
|
|
Term
| D2 is coupled to ______ G proteins |
|
Definition
|
|
Term
| when dopamine is around, how does it act through the D1 or D2 neurons to affect neuronal activity? |
|
Definition
naturally boosts D1 MSNs
naturally decreases D2 MSNs |
|
|
Term
| MSN input from cortex is ______ |
|
Definition
|
|
Term
| what can D2 MSNs do that D1 cannot? |
|
Definition
| send retrograde signal back to pre-synaptic glutamatergic cortical neuron to normally tamper the amount of input it gets |
|
|
Term
| main idea of PD symptoms: loss of LTD onto _______ |
|
Definition
|
|
Term
| stimulation of cortical inputs --> LTD of D2 MSNs only under what conditions? |
|
Definition
| in the presence of dopamine!! |
|
|
Term
| 7 steps in LTD of glutamatergic-D2 MSN synapse |
|
Definition
1. presynaptic neuron = glutamatergic input from cortex
2. mGluR5s on D2 MSNs coupled to Gq G proteins
3. cleaves precursors of retrograde messengers
4. bind Cb1 (cannabinoid) receptor in presynaptic terminal
5. these receptors are coupled to Gi
6. decrease calcium
7. decrease possibility of neurotransmitter release |
|
|
Term
| endogenous ligands of cannabinoid receptors |
|
Definition
|
|
Term
| exogenous ligands of cannabinoid receptors |
|
Definition
|
|
Term
| EPSCs measured in D2 MSN dendrite in striatum come from |
|
Definition
|
|
Term
| 5 steps of making retrograde messenger in D2 MSN |
|
Definition
1. glutamate
2. mGluR5
3. Gq
4. activate PLC (phospholipase C) IF dopamine is also present via the D2 receptors
5. generation of endocannabinoids which retrograde message to the presynaptic neuron |
|
|
Term
| 11 steps in breakdown of PLC cascade for LTD in D2 MSN |
|
Definition
1. PLC
2. cleaves PIP2 (phospholipid found in cell membrane)
3. results in IP3 & DAG (diacylglycerol)
4. DAG gets converted into endocannabinoids (ECBs) via DAG lipase
5. retrograde messenger
6. ECBs bind to Cb1 receptors
7. coupled to Gi
8. decreases voltage-gated calcium channels
9. less calcium in presynaptic terminal
10. less glutamate release
11. LTD! |
|
|
Term
| why does coincidence detection only happen in D2 & not D1 to activate the PLC? |
|
Definition
| D2-coupled receptors have Gi (D1 has Gs) which is necessary for the cascade that activates PLC! |
|
|
Term
| D2 MSNs pre-LTD = paired pulse _______ |
|
Definition
|
|
Term
| D2 MSNs post LTD = paired pulse _____ |
|
Definition
| facilitation BUT first pulse is smaller than original pre-LTD pulse (tells you LTD got induced ) & second pulse is smaller than original pre-LTD second pulse |
|
|
Term
| why do you do paired pulse experiments? |
|
Definition
| gives you insights into release probability of presynaptic terminal |
|
|
Term
| equation for PPR (paired pulse ratio) |
|
Definition
|
|
Term
| what is the current dopamine replacement therapy for PD |
|
Definition
|
|
Term
|
Definition
| death of SNc dopamine neurons |
|
|
Term
| problem of using dopamine replacement to treat PD |
|
Definition
| giving the patient dopamine is not specific for the SNc --> striatum pathway! |
|
|
Term
| 2 limitations of DBS to treat PD |
|
Definition
1. highly effective while stimulation is on, but symptoms return as soon as stimulation is turned off
2. masks symptoms but does not repair underlying brain dysfunction |
|
|
Term
| before DBS, what was done as a PD treatment? |
|
Definition
|
|
Term
| how does DBS work to treat PD? |
|
Definition
| input stimulating electrode into either subthalamic nucleus or GPi |
|
|
Term
| 2 challenges for current PD therapies |
|
Definition
1. not ideal for long-term care because they lose efficacy and/or cause side effects over time
2. new strategies must be developed to repair, not simply mask, brain dysfunction in PD |
|
|
Term
| main opportunity coming from basic research for PD therapies |
|
Definition
| new insights into which neural circuits are the best to target to maximize therapeutic benefit while minimizing side effects |
|
|
Term
| why can't you get specificity with DBS in striatum? |
|
Definition
| D1 & D2 cells are all intermingled |
|
|
Term
|
Definition
| a protein in our eyes that converts light energy into neuronal signals |
|
|
Term
|
Definition
| a protein found in algae that converts light energy into neural signals |
|
|
Term
| what is the benefit of having neurons express ChR2? |
|
Definition
| can be controlled with light pulses |
|
|
Term
|
Definition
| a technology that renders neurons genetically sensitive to light |
|
|
Term
| difficulty with optogenetics |
|
Definition
| need wavelengths that can penetrate deep into tissue (or even through the skull to be non-invasive!) |
|
|
Term
| how do you send light in optogenetic experiments? |
|
Definition
| fiberoptic cables chronically implanted |
|
|
Term
| benefit of optogenetic experiments |
|
Definition
| can do them in freely moving animals to observe how it affects behavior! |
|
|
Term
| how do you get channelrhodopsin into neurons? |
|
Definition
|
|
Term
|
Definition
| cation channel; used to excite neurons |
|
|
Term
|
Definition
|
|
Term
| bacteriorhodopsin & archaerhodopsin (Arch) |
|
Definition
|
|
Term
| what is the process where you use synthesized ligands to affect either channel or metabotropic receptor action? |
|
Definition
|
|
Term
| what is the process of inducing an ion channel that is not normally expressed in a mammalian cell that is activated by different wavelengths of light? |
|
Definition
|
|
Term
| 3 types of optogenetics channels |
|
Definition
|
|
Term
| what process works on the same properties as optogenetics but gates via ligands instead of light? |
|
Definition
|
|
Term
| in the dopamine-depleted state (Parkinsonian), there is an imbalance in _______ |
|
Definition
| direct/indirect pathway activity |
|
|
Term
| activating D1 pathways makes you ______ |
|
Definition
|
|
Term
| activating D2 neurons makes you ______ |
|
Definition
|
|
Term
| when ChR2 is expressed in D1 (direct pathway) --> ? |
|
Definition
|
|
Term
| When ChR2 is expressed in D2 (indirect pathway) --> ? |
|
Definition
|
|
Term
| what was the big empirical study of the paper we presented? |
|
Definition
| first empirical evidence of direct "go" vs indirect "no go" dichotomy |
|
|
Term
| how to make a mouse model of PD |
|
Definition
|
|
Term
| goal to treat PD in the paper we presented |
|
Definition
| increase activity in D1 MSNs --> restore ambulation in the PD mouse model to levels like pre-lesion! |
|
|
Term
| what does it mean that PD is caused by specific dopamine neuron loss? |
|
Definition
| SNc dopamine neurons die; VTA dopamine neurons do not |
|
|
Term
| why can't you get cell-type specificity with just stimulating electrode of DBS? |
|
Definition
| direct & indirect pathway neurons are all right next to each other |
|
|
Term
| limitations of L-DOPA to treat PD |
|
Definition
| patients can only tolerate it for a few years & then side effects become worse than the disease itself |
|
|
Term
| limitations of DBS to treat PD |
|
Definition
| very intense surgery & only works when stimulator is on |
|
|
Term
| overactivation of D2 --> ? onto GPe |
|
Definition
|
|
Term
| why would stimulating GPe theoretically rescue movement in PD? |
|
Definition
| in PD, GPe is getting overly inhibited so this should help relieve it |
|
|
Term
| what was the result with global GPe stimulation in PD? |
|
Definition
| immobility did not go away during GPe stimulation |
|
|
Term
| does the GPe contain different types of neurons? |
|
Definition
|
|
Term
| stimulating GPe PV neurons --> ? in PD |
|
Definition
| long-lasting rescue of motor movement in PD mouse model |
|
|
Term
| why does cell-specific stim of GPe work to relieve PD but global stim doesn't? |
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Definition
| non-PV neurons (Lhx6) interfere or block the therapeutic effects of PV stimulation |
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Term
| put Arch in Lhx6 neurons --> ? in PD |
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Definition
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Term
| what does it mean that there is a scaling problem in translating optogenetics into humans? |
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Definition
| injecting a virus into the mouse brain --> you can use the tiniest amount of a virus but it won't spread enough to be really effective in human brain |
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Term
| how are researchers trying to get around the problem of light delivery into the brain to use optogenetics in humans? |
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Definition
| shifting opsins to be responsive to far-red --> can shine light of that wavelength actually through the skull |
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Term
| why is optogenetics so helpful as a research tool? |
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Definition
| find out which circuits we need to target & use human-relevant therapeutics to target those circuits |
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Term
| why would conventional DBS in GPe not work to treat PD? |
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Definition
| we would be stimulating all GPe neurons --> no net effect |
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Term
| What change to DBS in GPe made it work in relieving PD symptoms? |
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Definition
| changing DBS to be brief stimulations |
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