Final Flashcards
Central Pattern Generators
Spinal (cranial) or motor circuits that control rhythmic behaviors
Feedback Inhibition
Flexors may excite extensors, which in turn inhibit the flexors to shut them off, depriving the extensors of their own excitatory input
-This simple feedback inhibition circuit can generate motor rhythms
Where is the primary motor cortex?
Most caudal part of the frontal cortex, just rostral to central sulcus
Stroke when a blood vessel is blocked by an embolism or blood clot, starving the brain of oxygen and glucose. If patient survives the stroke, only parital recovery
Ischemia
Caused when blood vessel bursts and bleeds into the brain, causing inflammation but not as much neuronal death. Higher risk of death during the stroke, but better recovery of function if the patient survives.
Hemmorage
What kind of memory problem did patient H.M have? What were the symptoms?
Total antero-grade amnesia for all declarative facts learned post-surgery
temporally-graded retrograde amnesia - better memory for “declarative” information acquired long before
surgery than recently before surgery
What kind of memory was normal in H.M and how was that tested?
Procedural memory and motor tasks were normal. H.M was able to improve at a memory task
What part of H.M.’s brain was removed and why?
Medial temporal lobe removed to treat severe epilepsy
What are the two kinds of declarative memory?
semantic memory (generalized memory for facts and info) Episodic memory - detailed autobiographical memory of event sequences from past
What are the three types of nondeclarative (procedural) memory?
Skill learning—learning to perform a task requiring motor coordination (example: eyeblinkconditioning). • Priming—repetition priming—a change in stimulus processing due to prior exposure to the stimulus. • Conditioning—the association of two stimuli or of a stimulus and a response (examples: eyeblink conditioning, fear conditioning, operant conditioning, etc.).
How does the delayed non-match-to-sample task work?
Monkey is presented with two objects, food is hidden under one after the monkey finds the food, a short delay occurs, then the monkey gets the two objects again but this time the food is hidden under the other object.
How do monkeys perform at the non-match-to sample task and how do brain lesions impact their performance?
- Normal monkeys are very good at the task
- Hippocampus lesions impair performance after long delays
- Prefrontal cortex lesions impair performance after short delays
Other than the hippocampus what other brain region lesions impair performance?
entorhinal cortex, parahimpocampal cortex, perirhinal cortex
How do hippocampal lesions affect contextual fear condition vs. tonal fear conditioning?
hippocampal lesions reduces contextual fear conditioning but not tonal fear conditioning
Do hippocampal lesions impair recent or distant memories? Is it different for rats and humans?
Hippocampal lesions impair recent but not distant memories in both rats and humans
Is the rat hippocampus proportionally smaller or larger than the human hippocampus and why?
Proportionally larger because rats have a much smaller cerebral cortex
What are the three major subdivisions of the hippocampus and what do they do?
- The dentate gyrus is involved in pattern separation
- The cornus ammonu3 is involved in pattern completion (filling in missing information in a pattern to facilitate later recognition)
- Cornus ammonu1 - main output circuit of the hippocampus
What are the parts, pathways and order of the tri-synaptic loop circuit?
Medial Entorhinal cortex — performant path —> dentate granule cells —Mossy fibers—> CA3 pyramidal cells —-Shaefer collaterals —-> CA1 pyramidal cells -> subiculum pyramidal cells —-> Medial entorhinal cortex
What kind of neurons become active when an organism needs to be motivated to spend energy and act?
Mesolimbocorticaldopamine neurons in the VTA
When an actual outcome was better than expected outcome
Positive prediction error
When an actual outcome was worse than expected outcome
Negative prediction error
When an animal learns which action will ultimately produce pleasure. (Action-outcome associations)
Instrumental learning
A signal that an action will produce an outcome
Discriminative stimulus (DS)
Cue that something negative or positive is about to happen
Conditional stimulus (CS)
How to rewards affect dopamine neuron responses in trained and untrained animals?
- In untrained animals, dopamine neuron increases firing rate when reward occurs (unexpected)
- In trained animals, the dopamine neuron increases firing rate during conditional stimulus (cue) but not during actual reward delivery
- During omission trial, dopamine neuron decreases firing rate below baseline if the reward does not appear when its expected
What was the result of the dopamine, food study?
After VTA lessioning, Rats were less likely to push a lever multiple times to get food but not less likely to push it once. This provides evidence for the incentive theory of dopamine release
What are the three non-mutually exclusive theories of dopamine as related to motivation?
- Reward Theory
- Prediction-error theory
- Incentive theory
A trained rat continuing to press a lever for food even after it has been adequately fed is an example of what type of learning?
Stimulus-action association or habit learning
What brain regions are involved in the goal-directed system?
-Prefrontal cortex
-Orbitofrontal cortex
-Hippocampus
-Nucleus Accumbens (ventral striatum)
Dorsolateral striatum
Term for an animal predicting what would happen if it followed a particular path
Model-based planning
How does long-term potentiation strengthen a synapse and what chemical pathway does it use to do that?
Greater concentrations of calcium trigger a chemical response that activates a glutamate receptor creating gene. When the cell fires and than receives glutamate it triggers the creation of AMP glutamate receptors
What types of cells have been discovered the entorhinal cortex and what do they do?
Grid cells in the entorhinal cortex fire like nodes of a hexagonal grid
-Border cells fire when the rat is approaching a barrier such as a wall in its cognitive map
what are place cells, when do they fire, where are they located in the brain and what is their firing rate?
- spatially tuned neurons in CA1 & CA3
- cell fires when the rat visits a preferred location, called the cell’s place field
- What rhythm to place cells fire at (8 Hz)
How has long-term potentiation been tested in a vat?
At baseline (PRE), each stimulus
pulse produces a small EPSP in CA1. After a strong highfrequency stimulus (HFS; 100 Hz train of electrical pulses), each
stimulus pulse produces a much larger EPSP in CA1 (POST)
How has long-term depresssion been tested in a vat?
At baseline (PRE), each stimulus
pulse produces a small EPSP in CA1. After a weak low
frequency stimulus (LFS; 1 Hz train of electrical pulses), each
stimulus pulse produces an even smaller EPSP in CA1 (POST)
How does long-term potentiation use neural coincidence detectors?
-At rest NMDA glutamate receptors have a Mg2+
that blocks the influx of cations to the intracellular
space
-Depolarization of the cell membrane removes the
Mg2+
-If the presynaptic cell releases glutamate during
depolarization, the NMDA receptor creates a
influx of calcium to the inside of the cell
How were place cells tested with rats in water?
In the Morris water maze, rats are placed in water and must find a hidden platform. When removed and then replaced in the water rats take less time to find the platform
What happens to place cells when the environment that rat has already explored changes?
The place cells change their firing pattern to reflect changes in the environment
-Different place cells change based on different contextual clues (e.g. olfactory vs. visual)
How does the brain consolidate information recorded in the recent past?
- When the rat is asleep or not-moving in the maze, place cells in the hippocampus fire in the same sequence as they did when recording a new memory but much faster
- Sometimes the order is faster and sometimes it is slower
What is one hypothesis why dream time seems to occur faster than real time?
The brain replays experiences faster (the actual sequence of cell firing is faster) when it is not constrained by motor realities in sleep
How are cells in the hippocampus organized?
They are not topographically organized and the centers are randomly distributed throughout the cognitive map
What kind of memory does the morris water maze test?
Declarative memory
Steps of the trisynaptic pathway?
Entorhinal cortex -> dentate gyrus -> CA3 -> CA1
How many bones are in the human body?
206
What controls skeletal movements?
skeletal muscle
Each muscle is a large bundle of many smaller ______
muscle fibers
_____ connect muscle and bone
tendons
Many skeletal joints are controlled by a pair of two _____ _________
antagonistic muscles
__________: contraction bends the joint (example: ____)
flexors, bicep
_______ :contraction straightens the joint (example: ______)
extensors, tricep
Muscles exert force by _______ (shortening of the fibers); they can only ____ a limb, not ____ it!
force by contracting
call only PULL a limb not Push
Running through the center of the muscle fiber is a bundle of protein filaments called a ________
myofibril
What are the two kinds of protein that compose a muscle fiber and what do they do?
- Actin: A cytoskeletal protein
- Myosin: A motor protein that grabs actin and “walks” along the actin filament
Each muscle fiber is a single large cell with many ______
nuclei
The muscle fiber is divided into segments called __________
sarcomeres
Myosin heads can shorten the sarcomeres by ___________________________________
grabbing actin filaments and drawing them together
A _______ is a single motor neuron plus all of the muscle fibers that it contracts
motor unit
Each motoneuron contacts ______, but each muscle fiber receives input from ______ motoneuron
multiple motorfibers that each receive input from only one motoneuron
Motor neurons in the spinal cord send their axons to muscle fibers, where they make synapses called ________
neuromuscular junctions
When the motor neuron fires an action potential, ______ is released at the NMJ
Acetylcholine
ACh binds to________ on the muscle fiber, causing ____ to enter
nicotrinic receptors; causing Na+ to enter
When Na+ channels open on the muscle fiber it does which three things:
- Opens calcium channels
- Fires an action potential
- Ca2+ enters the fiber, and this causes myosin to pull actin filaments together
Motor neurons are the __________ through which the brain and spinal cord control muscles.
final common pathway
Motor neurons release only ___ but they respond to a tremendous variety of synaptic transmitters, both ___________, released by the diverse inputs that each motor neuron receives.
Ach, excitatory and inhibitory
_______ carry motor commands from brain to body
ventral roots
How many pairs of nerves emanate from the spinal cord?
31
Motoneurons reside where?
Gray matter of the ventral horn of the spinal cord
Motor axons exit the ______ through the_______ to contact muscles in the head and face
brainstem; cranial nerves
What are the three primary sources of input to motoneurons and what do they do?
- The pyramidal motor system provides motoneuron inputs that initiate and control voluntary movements.
- The extrapyramidal motor system modulates motoneurons by fine tuning movements
- Sensory and proprioceptive neurons in the dorsal root ganglion provide motoneuron inputs (via interneurons in the dorsal horn) that mediate simple motor reflexes and central pattern generation.
The ________ is an automatic (involuntary) response to a painful stimulus
spinal withdrawal reflex
The withdrawal reflex can involve as few as ____ synapses
3
Central Pattern Generators
- motor circuits that control rhythmic behaviors
- receives tonic input from motor cortex, and converts it into phasic output to the muscles
- Sensory & proprioceptive feedback help to pace and control the motor rhythm
What sensory or motor singlas are lost when the right or left side of the spine is transected?
Motor: Loss of all motor function ipsilateral to the injury; contralateral function is spared
Sensory: Loss of contralateral nociception, ipsilateral proprioception and discriminative touch
When back half of spine is transected
Motor: Bilateral loss of voluntary motor function; olivospinal and vestibulospinal lpathways are spared, but don’t have much to do anymore
Sensory: Bilateral loss of proprioception& discriminative touch, no loss of nociception
Treatments for paralyzed patients
- implant a stimulator device that can electrically activate spinal CPGs, and thus substitute for the function of the lost pyramidal motor pathway
- Another strategy is to record neural activity from motor cortex to sense when motor commands are being delivered to the spinal cord, and deliver these command to robotic limbs / exoskeletons instead of to the muscles
How is the motor cortex organized and how are different muscles represented?
- topographically mapped to control muscles in different parts of the body
- Motor homunculus
What were the results of a Cerebral Hemorrhage in Right Primary Motor Cortex?
- Patient’s left leg, arm, and wrist were completely paralyzed after the stroke (other limbs not affected)
- Over 3 months, patients recovered function in wrist, arm, and leg (in that order)
- After recovery, patient was able to walk and return home to live independently
What is the difference between a supinated and a pronated grip
Fingers face up in supinated grip and face down in pronated grip
How does neuron firing in M1 correlate with movement
- Cell is excited before and during movement in the preferred direction
- Cell is inhibited before and during movement in the antipreferred direction
- Grip position does not matter
What is the canonic circuit in the cerebellum?
-The circuit receives specific types of sensory inputs and sends motor outputs to motoneurons that control different body limbs
What are the three steps in the Unconditioned Eyeblink Reflex and what do they do?
1) A mildly aversive unconditioned stimulus(US) such as an airpuff or weak shock is delivered to the skin of the eyelid, activating 1st order somatosensory receptor neurons of the ophthalmic nerve.
2) Somatosensory neurons activated by the US project to 2ndorder neurons in the trigeminal nucleus (one of the cranial sensory nuclei). These trigeminal neurons send their efferents to 3rd order motor neurons in the cranial facial motor nucleus.
3) The cranial facial motor nucleus contains motoneurons that send axons directly to the neuromuscular junctions of the eyelid muscles, which then produce the unconditioned response (UR) of blinking the eye.
positive reinforcing unconditioned stimulus
appetitive unconditioned stimulus
negative reinforcing unconditioned stimulus
aversive unconditioned stimulus
The nervous system learns to expect the US when the predictive CS is encountered
Pavlovian conditioning
A Pavlovian CR is typically a ___________ that animals innately perform when they expect the US
reflex behavior
Term for stage of conditioning when US elicits a UR from the subject, but the CS elicits no response
Pretraining (Baseline)
Term for stage of conditioning when CS and US are paired repeatedly so that the subject learns the CS predicts the US.
Training (Acquisition)
Term for stage of conditioning when the CS is presented without the US and the subject generates a CR
Testing
Term for stage of conditioning when the CS is repeatedly presented by itself so that the subject learns the CS no longer predicts the US. The CR diminishes and finally disappears.
Extinction
What are the five parts in the conditioned ear-to-eyelid pathway and what parts of the nervous system are used?
1) stereocilia -> spiral ganglion -> cochlear nucleus
2) Pontine nucleus -> Interpositus nucleus -> Red nucleus
3) Ophalmic nerve -> somatosensory neuron -> Trigeminal Nucleus
4) Auditory perception (CS) meets eyelid (US) at cranial facial motor nuclei
5) When both responses hit cranial facial motor nuclei the eyelid muscle contracts
What is the name of the fibers connecting the poutine nucleus and the interpositus nucleus?
Mossy fibers
Which 3 brain regions did not respond to the CS before conditioning but acquired a response to the CS in tandem with acquisition of the behavioral CR?
Interpositus nucleus and the red nucleus
How does the pontine nucleus respond to auditory stimulation before ear-to-eyelid conditioning? After?
The pontine nucleus is activated by auditory stimulation before and after ear-to-eyelid conditioning
Ear-to-eyelid conditioning suggests there is s______ ______ in the interpositus’ ______ _______
mossy fiber from the pontine nucleus
What brain region trains the ear-to-eyelid conditioning and how? Hint: it’s a returning character from last season
The inferior nucleus synapses with the trigeminal nucleus and grows climbing fibers to the interpositus nucleus
How do we know the inferior olive creates the ear-to-eyelid pathway?
Correlation Test: Neurons in the IO respond to the US
Necessity Test: When IO is lesioned, the CR functions as if US is absent
• Pre-training lesions of the inferior olive completely prevent acquisition of the eyeblink
CR (but do not interfere with the eyeblink UR!!! Only the CR is affected!!!)
• Post-training lesions cause extinction of the CR during subsequent CS-US pairings, as if the US was not being delivered anymore
• Sufficiency Test: Electrical stimulation of the IO can substitute for the US; if the CS is paired with IO stimulation, an eyeblink CR will develop even though the eyelid is not being shocked or puffed!
Pre-training (baseline) neural response to the CS
When the CS alone is presented before training, pontine nucleus neurons fire and release glutamate onto interpositus neurons
• The glutamate binds to both AMPA and NMDA receptors, but only the AMPA receptors pass current, because the NMDA receptors are blocked by Mg2+
• Sodium entry through AMPA receptors generates an EPSP, but this EPSP is too small to trigger an action potential in the interpositus neuron, because there are very few AMPA receptors in the mossy fiber synapse, and therefore it is a WEAK synapse
What two things happen when the US alone is presented before training and what does not happen?
- The inferior olive fires and release glutamate onto interpositus neurons
- The glutamate binds to AMPA receptors, which generate an EPSP, and this EPSP is large enough to trigger an action potential in the interpositus neurons, because there are lots of AMPA receptors in the climbing fiber synapse
- Depolarization of the interpositus neurons pops the Mg2+cork off of the NMDA receptor at the mossy fiber synapse, but the receptor does not open because it is not binding glutamate
What two things happen during training and what third thing does that allow?
- When the CS and US are paired during training, the CS causes pontine nucleus neurons to fire and release glutamate onto WEAK interpositus synapses, and at the same time, the US causes inferior olive (IO) neurons to fire and release glutamate onto STRONG interpositus synapses
- Strong US-evoked depolarization of the interpositus neuron by the climbing fiber synapse kicks the magnesium block off of the NMDA receptor at the mossy fiber synapse, at the same time that he NMDA receptor is binding CS-evoked glutamate from the pontine neuron
- The NMDA receptor can now pass current, and it allows calcium (Ca2+) to enter the interpositus neuron
What are the chemical substrates of long-term potentiation in the ear-to-eyelid circuit?
- Calcium entry through NMDA Rreceptors activates a molecule called calmodulin(CAM), which in turn activates a molecule called CAM kinase II (CAMKII)
- CAMKII triggers a chemical signaling cascade that leads to the insertion of more AMPA receptors into the postsynaptic membrane of the mossy fiber synapse
- These additional AMPA receptors make the synapse stronger, a phenomenon known as “long term potentiation” (LTP) of the synapse
What are one neural correlate for Hebbian coincidence detectors?
NMDA receptors because the cell needs to be depolarized to push out the Mg+2 ion blocking the calcium channel and glutamate needs to attach to the receptor in order to activate it.
NMDA receptors in the interpositus are necessary for _______ but not ________ of the eyeblink CR
acquisition, expression
What drug is delivered to impair NMDA receptors? What kind of drug is it and where is it delivered?
NMDA receptor antagonist drug (AP5) delivered to the interpositus nucleus
What part of the brain seems to time and sculpt conditional responses?
the anisoform and paramedian lobules of the cerebellum
________ dendrites in conditioned eyeblink reflex connect to ______ in the cerebellar cortex
Mossy fibers; granuie cells
_______ cells in cerebellar cortex inhibit _______ nucleus
Purkinje cells in cerebellar cortex inhibit interpositus neuron
When the pontine is activated by the CS, it triggers a sequence of _____ cells to fire in the cerebellum
The granule cells excite ________, which in turn inhibit the ___________, and this prevents a CR from occurring
When the pontine is activated by the CS, it triggers a sequence of granule cells to fire in the cerebellum
The granule cells excite purkinje cells, which in turn inhibit the interpositus, and this prevents a CR from occurring
______ _______ project to the cerebellar cortex.
Simultaneous activation of a granule cell with a climbing fiber will _______ that granule cell’s synapse onto the Purkinje cell
Climbing fibers will project to the cerebellar cortex.
Simultaneous activation of a granule cell with a climbing fiber will weaken that granule cell’s synapse onto the Purkinje cell
Why are your muscles not constantly spasming?
The global pallidus internal, part of the basal ganglia, inhibits the ventral thalamic nuclei which prevents the thalamus from keeping the motor cortex continually stimulated
What is term for when a constant inhibition signal is being sent and only interrupted occasionally
tonically inhibited
What is the term for brief non-constant inhibition signaling
phasic inhibition
What are 3 defensive patterns of prey and how do they manifest?
Anxiety: knowledge motivates prey to avoid danger
Fear: Prey sees predator and flees
Panic: Prey flees to evade attack
What are the 3 phases of predation?
Procurement, pursuit and strike
What brain regions mediate the three fear behaviors?
Anxiety - prefrontal cortex + amygdala
Fear: Amygdala
Panic: Periaqueductal gray
Four functions of periaqueductal gray
Freeze
Flight
Analgesia
Automatic changes in heart rate/blood pressue
Which part of the brain derives flight responses
Dorsal periaqueductal gray columns
Which part of the brain derives freezing responses
ventral periqueductal gray columns
What are two ways that innate anxiety can be measured in mice?
Bright lights and open spaces
What is one test of a mouses’ innate anxiety and how did the mouse respond?
In open-field paradigm mice spend more time walking around periphery than center because of predators
People and animals can be trained to be afraid of cues that predict danger, a process known as___________________
People and animals can be trained to be afraid of cues that predict danger, a process known as Pavlovian fear conditioning
The central and medial nucleus of the amygdala together are sometimes referred to as the ________ or the ____________ and contains ________ projection neurons
The central and medial nucleus of the amygdala together are sometimes referred to as the “extended amygdala” or the “striatal amygdala” and contains inhibitory projection neurons
Two pieces of evidence that amygdala mediates fear response in humans
Humans participants had a higher BOLD response in the amygdala when viewing fearful faces over happy faces
-Amygdala lesioned humans don’t find usually fear inducing stimuli to be scary
What are the three parts of the cortical amygdala?
Lateral
Basal
Accessory Basal Nucleus
The lateral and basal nucleus together are often referred to as the ________ amygdala
The lateral and basal nucleus together are often referred to as the basolateral (BLA) amygdala
_________ cells are the main fear-inducing output of the amygdala.
Central amygdala
The cortical amygdala has _______ projection neurons
The cortical amygdala has excitatory projection neurons
What is channelrhodopsin?
a sodium channel sensitive to blue light, which causes sodium to enter and depolarize the cell.
What is halordhospin?
a chloride pump
sensitive to yellow light,
causes chloride to be pumped in
hyperpolarizing the cell.
What is Archaerhodopsinis?
a proton pump sensitive to green light, which causes hydrogen ions (protons) to be pumped out, hyperpolarizing the cell.
Ca2+ not only activates _____ but also triggers adenylyl cyclase to convert ____ to _____(remember that olfactory g-protein receptors also did this in olfactory receptor neurons?)
Ca2+not only activates CAMKII, but also triggers adenylyl cyclase to convert ATP to cAMP(remember that olfactory g-protein receptors also did this in olfactory receptor neurons?)
- cAMP then activates cAMP-dependent protein kinase (better known as PKA), which in turn phosphorylates _____ - _______ ____ _____ (___)
- _____ translocates to the soma and enters the nucleus of the LA neuron, where it activates a transcription factor called ____
- cAMP then activates cAMP-dependent protein kinase (better known as PKA), which in turn phosphorylates mitogen-activated protein kinase (MAPK)
- MAPK translocates to the soma and enters the nucleus of the LA neuron, where it activates a transcription factor called CREB
______ activates gene transcription in the nucleus of the cell, producing mRNA that is transcribed into new proteins
• These new proteins provide the raw “building materials” for constructing new _____ ______ on the LA neuron
CREB activates gene transcription in the nucleus of the cell, producing mRNA that is transcribed into new proteins
• These new proteins provide the raw “building materials” for constructing new dendritic spines on the LA neuron
Infusion of _______ (protein synthesis blocker) into amygdala during tone-shock pairing impairs ___-term memory (LTM) but not ____-term memory (STM) for the CS-US association, as assessed by tone-evoked freezing _ hour versus ___ hours after training
Infusion of anisomycin (protein synthesis blocker) into amygdala during tone-shock pairing impairs long-term memory (LTM) but not short-term memory (STM) for the CS-US association, as assessed by tone-evoked freezing 1 hour versus 24 hours after training
• A: Rats with hippocampal lesions do not freeze to the _____ but they do to the ____ ____ ___
• A: Rats with hippocampal lesions do not freeze to the training context but they do to the auditory tone CS
Neurons in the ____ nucleus of the amygdala receive nociceptive inputs that are excited by the footshock US, as well as inputs from neurons in the ____ ________ that are thought to fire selectively in specific contexts. Prior to fear conditioning (baseline), the context input synapses onto B neurons are weak. Pairing the CS and context strengthens these synapses.
Neurons in the basal (B) nucleus of the amygdala receive nociceptive inputs that are excited by the footshock US, as well as inputs from neurons in the ventral hippocampus that are thought to fire selectively in specific contexts. Prior to fear conditioning (baseline), the context input synapses onto B neurons are weak. Pairing the CS and context strengthens these synapses.
What are the three ways that an extinguished response to a CS can return and what is required for each way to be activated?
Renewal: Responding returns when a CS is encountered in a context other than where it was extinguished
Reinstatement: Responding returns upon re-encountering (even just once!) the aversive US.
Spontaneous recovery: Responding just comes back on its own after the passage of time
Which brain region enhances extinguishing of fear conditioning and which brain region impairs extinguishing?
Infralimbic (or ventromedial) region of the pre-frontal cortex enhances extinguishing
Pre-limbic (or dorsomedial) region of the pre-frontal cortex impairs extinguishing
How does Infralimbic pre-frontal cortex (IL) inhibit freezing behavior?
Infralimbic pre-frontal cortex sends excitatory axons to the basomedial amygdala which then gets excited and inhibits the central amygdala.
When the central amygdala is excited it can’t inhibit the area of the periaqueductal gray that is inhibiting the ventral periaqueductal gray and so less freezing happens
How do we know that the infralimbic pre-frontal cortex is enervating the basomedial amygdala?
When an anterograde tracer molecule (green) was injected into PL (or dmPFC), very few axon terminals were labeled in the basomedial amygdala (BMA). But many axons were labelled when the tracer was injected into IL (or vmPFC).
What is the optogenetic evidence that the basomedial amygdala is inhibiting fear conditioned freezing?
When basomedial amygdala cells were infected with channelrhodospin, stimulating these cells with blue light suppressed conditioned freezing
What kind of people cannot be fear conditioned?
People with lesions in the amygdala
What kind of threat responses are amygdala lesioned people capable of and why?
Amygdala lesioned people can panic to stimulus like asphyxiation (ex. inhalation of carbon dioxide) because panic is controlled by the ventral periaqueductal gray and NOT mediated by the amygdala
The _____ ______ _____ inhibits the anxiety and fear inducing _____ _____ _____
The central lateral amygdala (CeL) inhibits the anxiety and fear inducing central medial amygdala (CeM)
Optogenetic activation of the excitatory projection from ______ _______ to _____ _____ ______ increases exploration of open spaces, indicating a reduction in anxiety because the ______ _____ _____ inhibits the _______ _______ ______
Optogenetic activation of the excitatory projection from basolateral amygdala (BLA) to the central lateral amygdala (CeL) increases exploration of open spaces, indicating a reduction in anxiety because the central lateral amygdala (CeL) inhibits the central medial amygdala.
Deep brain stimulation applies electricity to temporarily _____ the ______ ______ and the _______ _______ ______ to treat Parkinson’s disorder
Deep brain stimulation applies electricity to temporarily inhibits the subthalamic nucleus and the globus pallidus internal to treat Parkinson’s
What are three disorders that are currently treated with deep brain stimulation and how is it used?
Depression: anterior cingulate, globus, pallidus internal, subthalamic nucleus, Lateral habenula, ventral capsule and ventral striatum
Chronic Pain: periaqueductal gray
Epilepsy: Can monitor brain activity and apply corrective stimulation
What are the four brain areas that have been stimulated to reduce depression?
Anterior cingulate
Globus Pallidus Internal and Subthalamic Nucleus
Lateral habenula
Ventral capsule and ventral striatum
What has been the results of DBS application to the anterior cingulate and the globus pallidus + subthalamic nucleus in depression treatments?
- Anterior cingulate cortex (Brodmann area 25)
- BROADEN clinical trial (Mayberg and colleagues) failed futility analysis in 2014 and was halted
- prognosis for future trials is uncertain
- STN/Gpiin Parkinson’s patients
- Although this DBS treatment is broadly effective for treating motor symptoms, evidence for relief of depression is mixed at best
What has been the results of DBS application to the lateral habenula in the ventral capsule/ventral striatum (patient with Parkinson’s)?
- Lateral Habenula
- Remission reported in a single-patient trial (Sartorius et al. 2010)
- Rescue of learned helplessness reported in a rodent model via repeated electrical stimulation of habenula to deplete neurotransmitter release (Li et al., 2011)
- Ventral capsule / ventral striatum (VC/VS) in Parkinson’s patients
- Remission reported in a single-patient trial (Williams et al. 2015)
- Patient was implanted with STN DBS that improved tremor but not OCD/depression
- OCD/depression improved following additional DBS implant in VC/VS
What disorders are treated with closed-loop neuromodulation and how is it used?
Cardiac pacemakers are used to treat cardiac arrhythmias and neuropaces are used to treat epilepsy
Possible potential for depression
_____ _______ _______ studied walking behavior in cats with spinal cord injuries. In 1911, he was the first scientist to discover that walking is controlled by _______ ________ _______ in the spinal cord.
Thomas Graham Brown studied walking behavior in cats with spinal cord injuries. In 1911, he was the first scientist to discover that walking is controlled by central pattern generators in the spinal cord.
What three procedures did Thomas Graham Brown enact to induce spinal cord injuries in cats?
- Spinal cord was completely transected at T13 • Front feet were placed on a stationary platform
- Back feet were placed on a moving treadmill
- Movement of the leg limbs and joints were tracked by reflective markers
What are the two phases of walking?
- Swing phase: foot is lifted from the ground and swings forward
- Stance phase: foot is planted on the ground and pushed backward (to propel the body forward)
- Brown found that spinal cord injury _____ ___ ______ __ _______ in both the swing & stance phases
- However, the walking rhythm_________________
- This shows that ________________ and ____________
- Brown found that spinal cord injury reduces the range of motion in both the swing & stance phases
- However, the walking rhythm remains intact after injury, with preserved continuous alternation between swing + stance phases
- This shows that the CPGs for walking are in the spinal cord, and they do not need input from the brain to generate motor rhythms!
- Sensory & proprioceptive feedback to spinal CPGs is essential for synchronizing the swing and stance phases of the walking rhythm
- If sensory inputs to the spinal cord are lesioned by cutting the ____ ____ before a spinal cord injury, then the walking rhythm ______ persist after the injury
- Hence, proprioception plays an important role in both _______and _______________________
- Sensory & proprioceptive feedback to spinal CPGs is essential for synchronizing the swing and stance phases of the walking rhythm
- If sensory inputs to the spinal cord are lesioned by cutting the dorsal root before a spinal cord injury, then the walking rhythm will NOT persist after the injury
- Hence, proprioception plays an important role in both normal walking and post-injury CPG rhythm generation
Why are rats and mice typically used for spinal cord injury research?
They are the lowest phylogenetic mammal
What are 3 strategies for reconnecting the severed spinal cord?
- Inject neurotrophic factors (such as NGF or BDNF) to trigger new growth and connections
- Insert stem cells that can grow and differentiate into new neurons that send axons across the break
- Transplant glial cells (for example, olfactory ensheathing cells, or OECS) to promote regeneration
What are the two kinds of potency of stem cells?
Pluripotent: Can make all types of specialized cells in the body Embryonic stem cells are pluripotent
Multipotent: Can make multiple types of specialized cells, but not all types Tissue stem cells are multipotent
What are the four stages of cell differentiation in the nervous system?
- Pre-neural plate: embryo is composed of pluripotent stem cells
- Neural plate: multipotent cells can become neurons or glial cells
- Neural plate divides into precursor neurons and precursor glial cells
- Glial cells divide into astrocytes or oligodendrocytes
- In neurogenesis, neural precursors become neurons
Where are the only two places omni and pluri potent cells harvested from?
blastocytes or fetuses
Where can glial or neuronal precursor cells be harvested from?
fetal tissue or from the patient’s own organs
Harvested stem cells are injected into the spinal cord near __________, often _____________, in the hopes that they will differentiate into new spinal neurons (motoneurons, interneurons) and supporting glial cells (such as OECs)
Harvested stem cells are injected into the spinal cord near the site of injury, often along with growth factors, in the hopes that they will differentiate into new spinal neurons (motoneurons, interneurons) and supporting glial cells (such as OECs)
How have stem cells been created and what is a potential problem with this mechanism?
- A retrovirus was used to add certain transcription factors to a somatic cell
- retroviruses used could interrupt tumor suppressor genes
_______________ can be transplanted into the spinal cord where they can promote regrowth of damaged spinal axons! This is a promising new therapeutic approach for spinal cord injury; OECS ______________ and ___________ to guide and promote the growth of their axons. They may be able to do a similar thing for spinal axons
Olfactory Ensheathing cells can be transplanted into the spinal cord where they can promote regrowth of damaged spinal axons! This is a promising new therapeutic approach for spinal cord injury; OECS release chemical signals and ensheath the axons of olfactory receptors to guide and promote the growth of their axons. They may be able to do a similar thing for spinal axons
Motor cortex neurons must receive “permission” from the ______ ______ to produce motor output
Motor cortex neurons must receive “permission” from the basal ganglia to produce motor output
The “permission signal” for movement comes through excitatory feedback inputs to motor cortex from the ____ _____: __ _______ ______ (__)
motor thalamus: the ventral thalamic nuclei (VTN)
The ventral thalamic nuclei are ______ inhibited by ______ neurons in the internal segment of the ______ (__)
The ventral thalamic nuclei are tonically inhibited by GABAergic neurons in the internal segment of the globus pallidus(GPi)
To initiate a movement, neurons must be ______ inhibited, which disinhibits the ventral thalamic nucleus permission signal
To initiate a movement, Globus pallidus internal neurons must be phasically inhibited, which disinhibits the VTN permission signal
The globus pallidus internal segment is inhibited by ____ _____ neurons (____ ____ ___) that express the __ dopamine receptor
The globus pallidus internal segment is inhibited by striatal projection neurons (spiny stellate cells) that express the D1 dopamine receptor
The Dorsal striatum is part of which larger brain structure
The Basal Ganglia
What is another name for the dorsal striatum?
Caudate putamen
Output neurons of the dorsal striatum are called ________ and they are _________ (send what kind of neurotransmitter?)
Output neurons of the dorsal striatum are called medium spiny neurons and they are GABAgenic
The ________ ________ (type of inhibition) inhibits the Globus Pallidus internal
Subthalamic nucleus tonically inhibits the Globus Pallidus Internal
The _____ _____ _____ segment is inhibited by striatal projection neurons (also spiny stellate cells) that express the __ dopamine receptor
The Globus pallidus external segment is inhibited by striatal projection neurons (also spiny stellate cells) that express the D2 dopamine receptor
What are the 3 major symptoms of Parkinson’s disorder?
- Resting tremor: in the early stages of the disease, limbs tremble when they are not being used (oscillating between direct/indirect?)
- Rigidity: Increased muscle tone and stiffness of the limbs (locked limbs caused by simultaneous direct/indirect commands?)
- Bradykinesia: slowness of movement, difficulty initiating movements (loss of the direct pathway?).
How does L-Dopa help people with Parkinson’s and what is the major problem with its long-term use?
Orally injesting L-dopa into the blood stream increases its abundance in the brain which means that the remaining substantia nigra pars compacta neurons can work twice as hard and produce closer to normal amounts of dopamine
-However as substantia nigra pars compacta neurons continue to die off and the patients develop a tolerance, higher levels of L-dopa are required and this can trigger symptoms like psychosis that are related to an overactive mesolimbocrortical system
Tyrosine is catalyzed into _____ by _____ ______, and ______ is then converted into dopamine by ______ _______ and _____ _____ _________
Tyrosine is catalyzed into Levadopa (or L-DOPA) by tyrosine hydroxylase, and L-DOPA is then converted into dopamine by DOPA decarboxylase and L-amino acid decarboxylase
To model Parkinson’s disease in mice, dopamine inputs to the striatum were destroyed by injecting ____________, a toxin that kills dopamine releasing neurons (so that D1 neurons become underexcited)
To model Parkinson’s disease in mice, dopamine inputs to the striatum were destroyed by injecting 6-hydroxydopamine (6-OHDA), a toxin that kills dopamine releasing neurons (so that D1 neurons become underexcited)
_______ is a gene that kills neurons when they express it
taCasp3: a gene that kills neurons when they express it
What was the necessity test for orexigenic properties of GABA neurons in the lateral hypothalamus?
- Researchers packaged the taCasp3 transgene in a virus, and conjugated it to a promoter that would cause it to be expressed only in GABA neurons
- The virus was then injected into LH, so that only the GABA neurons (but not other neurons) in LH would be killed
- It was found that LH GABA neurons were necessary for normal appetite
What was the sufficiency test for orexigenic properties of GABA neurons in the lateral hypothalamus?
- Appetite is stimulated by chemogenetic activation of GABA neurons in LH
- GABA neurons (but not other neurons) in LH were infected with a virus delivering hM3Dq
- When the modified mice are given CNO, they increase consumption of caloric liquid
How is the real time place preference test conducted?
Chanelrhodospin is added to Ventral tegmental area neurons using tyrosine hydroxalase promoter and can then be stimulated with green light.
- Rat is put in a square box and green light is turned on whenever it is one side of the box but not on the other
- The rat soon learns to stay on the side of the box where the light is on
How do Lateral hypothalamus GABA neurons stimulate hunger?
Lateral hypothalamus GABA neurons inhibit GABA neurons in the rostromedial tegmentum (RMTg) that inhibit DA projections from VTA to nucleus accumbens(NAcc)
How do opiates and cannaboids work to activate the reward circuit?
They block inihibition of VTA neurons by GABA neurons
How do amphetamine and cocaine work to activate the reward circuit?
The inhibit reuptake of catecholamines (dopamine, norepinephrine epinephrine)
How does nicotine work to activate the reward circuit?
stimulate dopamine release via excitation of DA neurons and inhibition of GABA neurons that block dopamine release
The weight loss drug, ________ is _ ___ ______ ________ which BLOCKS the same synapses that are excited by THC
Rimonabantis a CB1 receptor antagonist which BLOCKS the same synapses that are excited by THC
