In which region of the brain are the tight-junctions between capillary endothelial cells ABSENT; whats the significance?
- Circumventricular organs (i.e., area postrema, posterior pituitary)
- High permeability to circulating blood signals, allowing it to detect various chemical messengers in the blood and CSF
Activation of which of the following receptors is most likely to lead to a significant calcium influx?
A) AMPA receptor
B) NMDA receptor
C) GABA-b receptor
D) Kainate receptor
B) NMDA receptor
Which of the following is the most likely to occur in a patient deficient in P-glycoprotein at the blood brain barrier?
A) Measurable levels of penicilln in the CSF
B) CSF glucose levels below normal
C) CSF K+ levels higher than normal
D) Increased CSF protein concentration
A) Measurable levels of penicillin in the CSF
What are 3 major components of the BBB?
2) Pericyte = contractile!
3) Endothelial cell
Which ion does the NMDA vs. AMPA receptor cause the influx?
- NMDA —> Ca2+ influx
- AMPA —> Na+ influx
What are 5 molecules/types of molecules that move across the BBB via passive diffusion?
4) Unbound steroid hormones
5) Lipid soluble molecules
What is the transporter for glucose to move from the blood across the BBB; does it depend on insulin?
- NOT insulin-dependent
What is the role of the Na+-K+-2Cl- transporter at the BBB?
Moves all 4 ions OUT of the CSF
Role of the Organum vasculosum of the lamina terminalis (OVLT)?
Sensor for plasma osmolarity to trigger thirst/ADH release
Role of the Area Postrema?
Initiation of vomiting in response to chemotactic triggers
What is the clinical significance of the Circumventricular organs when it comes to toxins?
Areas are more sensitive to damage due to toxins in the blood because they lack tight junctions
The vasculature in the brain is innervated with _________ (pretty much the only place in the body)
Which ions are excitatory and which are inhibitory for ionotropic receptors on the post-synaptic membrane?
- Ca2+ or Na+ = cell depolarization and epsp occurs
- Cl- or K+ = hyperpolarization and ipsp occurs
What NTs activate the NMDA receptor and what does this cause?
What is the speed/duration of the EPSP produced?
- Glutamate and aspartate
- Allows Ca2+ influx
- Slow onset and prolonged duration
What are the modulatory sites on the NMDA receptor?
- Glycine binding site
- Mg2+ binding site
- PCP binding site
What are the functions of glycine, Mg2+, and PCP on the NMDA receptor?
- Glycine serves as a co-agonist; required for EAA (glutamate) to have a affect)
- Mg2+ blocks the channel; removed by depolarization
- PCP binds inside the channel, blocks the channel
What is the significance of both the AMPA and NMDA receptors working together to maintain EPSPs in the post-synaptic cell?
- AMPA provide fast depolarization
- NMDA receptors determine the duration of the depolarization
The AMPA receptor contains a binding site for which pharmacologic agent that inhibits the response to NT?
Metabotropic receptors are found on which parts of a synapse?
- Both pre- and post-synaptic location
- Pre-synaptically control the release of NT
Describe the recycling (re-uptake) system for EAA’s and the role of neurons and glia?
- Neurons and glia: use Na+-dependent secondary active transport and have high affinity for EAAs (glutamate)
- Glia: convert glutamate –> glutamine and release into ECF
- Neurons: take up the glutamine and convert back to glutamate
EAA re-uptake is ______ dependent
When excessive EAA is released leading to an increased intracellular [Ca2+] what 4 things are activated?
1) Phospholipase A2
2) Calcineurin (phosphatase)
3) Mu-calpain (protease)
4) Apoptotic pathway
What occurs with the activation of phospholipase A2?
- Release of arachidonate from membrane, which acts at ryanodine receptor on ER
- Release of Ca2+ from intracellular stores —> Unfolded protein response
- Imparied function of mitochondria
Activation of Mu-calpain (protease) with excessive EAA release causes what?
- Spectrin (structural damage to cell)
Activation of calcineurin leads to the activation of ______, which increases the synthesis of ______
Activation of calcineurin leads to the activation of NOS, which increases the synthesis of NO
Influx of excessive calcium causes disruption of mitochondrial membranes and initiates which cell death pathway?
Which cells are affected?
Apoptosis in any cell receiving synaptic input from the over active cell, even if the cell isn’t impacted by the original insult
Which NT acts on an ionotropic receptor in the area postrema and triggers vomiting?
Which NT produced in Substania Nigra and Ventral Tegmental Area (VTA)?
Which NT produced in the Locus Coeruleus?
Which NT produced in the Raphe nuclei?
Which NT produced in the Pedunculoponti tegmental and Laterodorsal nuclei?
Which NT produced in the Tuberomammillary Nucleus of the Hypothalamus?
What are the 2 pathways from the Reticular Activating System?
1) Dorsal - through the thalamus
2) Ventral - bypasses the thalamus
To move from a coma —-> arousal/wakefulness requires which NTs?
EAA an ACh
To move from arousal (wakefulness) —-> awarness requires which NT’s?
NE and Serotonin (5-HT)
To move from awarness —-> alertness which NT is required?
Which part of the brain is involved in the initiation of intended movement and suppression of unwanted movement?
Major function of the Premotor cortex?
- Determines whether it’s okay to move
- Identifies the goal and the motion required to meet that goal
Major function of the Supplementary motor cortex?
- Postural control
- Identifies the specific motor sequence required and plans the motions
- Changes tactics if necessary
Function of the S1 and S2 areas of the cortex?
- S1: initial processing - identify the charactrisitcs of wthat activated the receptors
- S2: stereognosis (ability to recognize an unseen object by touch), comparing 2 objects, ties to memory
What is the function of the parietal-temporal-occipital (PTO) association area?
Which pathway in the basal ganglia is lost in Huntington disease; leads to?
- Loss of indirect pathway
- Results in excess motion
To allow for motion the indirect pathway of the basal ganglia must be inhibited at th same time the direct pathway is activated, how is this accomplished?
- Dopamine from nigrostriatal neurons binds to D2 receptors
- D2 inhibits the neuron
How is the indirect pathway of the basal ganglia activated; leads to?
- ACh activates GABAergic input
- When active, inhibits motion
Function of the medial and lateral parts of the Spinocerebellum?
- Medial: postural control
- Lateral: correct ongoing motion
Function of the Cerebrocerebellum?
Planning of complex motion; motor memory
Input from the ______ is abolished in Parkinson disease, which has what 2 effects?
- SNPC input is abolished
- Direct pathway becomes difficult to activate
- Indirect pathway becomes overactive
Function of the Superior Olivary Nucleus and its medial/lateral aspects?
- Superior Olive: localization of the source of the sound
- Medial: detect intra-aural time difference
- Lateral: detect intra-aural volume difference (‘L’ = loud!)
Function of the Inferior Colliculus and Superior Colliculus?
- Inferior Colliculus: suppresses information from echoes
- Superior Colliculus: creates 3D map of where sound is
Which cortex provides a tonotopic map of the sound, loudness, etc?
Primary auditory cortex
Which cortex provides a complex map of sound, including harmonies, etc?
Auditory association cortex
Which otolith organs are essential for horizontal and vertical motion detection?
- Utricle = horizontal
- Saccule = verticule
What type of motion is detected by the horizontal (aka lateral), anterior, and posterior portion of the semicircular canals?
- Horizontal (aka lateral) = turning in circles
- Anterior = falling forward
- Posterior = falling backwards
The hair cells of the cochlea are surrounded by what?
What is the ion content of this fluid?
- High in K+/low in Na+
What are the major differences between Aδ and C sensory fibers of nociception?
- Aδ have a larger diamters (1-5um) and a faster conduction velocity; slightly myelinated = FAST, SHARP pain
- C fiber have a small diameter (0.2-1.5um) and a slow conduction velocity; unmyelinated; SLOW, DULL pain
What is the importance of the Insular Cortex in the central processing of pain?
Damage to this area causes what?
- Relays nociceptive input to limbic system
- Emotional component of pain
- Damage produces pain asymbolia - painful inout are recognized as painful, but not perceived as unpleasant
What is the difference between the Spinothalamic and Spinoreticulothalamic path in regards to processing of pain?
- Spinothalamic is for fast/sharp pain (Aδ)
- Spinoreticulothalamic for slow/dull pain (C fibers)
Why is the Spinoreticulothalamic path particularly important in regards to pain?
- This pathway has a synapse in the spinal cord at the level where the afferent enters the spinal cord
- Gating mechanism (gate theory of pain): non-nociceptive input from Aδ fibers (cutaneous) inhibit painful inputs via pre-synaptic inhibition
- Descending opioid inputs via raphe nuclei also act to decrease transmission at this synapse (also prescribed opioids)
Peripheral nociceptors can be activated by which chemicals; how does this affect the perception of pain?
- Substance P and Bradykinin
- Leads to sensitization of the nociceptor –> increased activation w/ similar stimulus –> PAIN PERCEIVED INCREASES
Role of V2 and V4 of the visual cortex?
V2 = depth perception (visualzing the shark in the random dot sterogram!)
V4 = color perception
Function of the dorsal visual pathway vs. ventral visual pathway?
- Dorsal = use of visual information in motion ( i.e., playing catch w/ friends)
- Ventral = higher cognitive processing using visual information (i.e., naming objects, etc..)
Function of the Lateral geniculate body?
- Eye movements!
- Detection of motion and intial processing (what’s the interesting stuff here)
Major function of the Primary Visual Cortex (V1)?
- Initial processing
- Identifying the edges/countours
- Columns: devoted to orientation of the lines in visual field
- Job: create a contour map of the visual field
- Blobs: initial color processing
High pitched sounds cause maximum bending where in comparison to low pitched sounds?
- High pitched = close to the oval window
- Low pitched = at the helicotrema
The muscle spindle is sensitive to ______ of the muscle
The ends of the muscle spindle contain what time of efferent neuron?
Gamma motor neuron; only influences the muscle spindle; controls sensitivity of muscle spindle
Which reflex detects the amounts of force in contracting muscle and causes inhibition if the force of contracting muscle could tear the tendon?
Golgi tendon organ reflex (inverse myotatic, autogenic inhibition reflex)
Differentiate between the group Ia and group II sensory afferent fibers of the musle spindle, what does each sense?
- Ia = length AND rate of change; innervates both the nuclear bag and nuclear chain; large and heavily myelinated
- II = length; innervates only the nuclear chain fiber; small and less myelin
Reflexes controlling eye movements when we fall/rotate are major actions and the central processing of these movements is related to what?
Suppressing the reflexes
What is the Presbyopia?
- Inability to change the shape of the lens (stiffness or inflexibility)
- Need a more round lens for near-vision and flat lens for objects in distance
Excessive activation of which receptor is seen after seizure/stroke/TBI?
NMDA receptor —> excessive Ca2+ influx —> initiates apoptosis
What is the inhibitory receptor of the CNS and differentiate the 2 types.
- GABA-a - ionotropic (chloride)
- GABAb - metabotropic
Histamine acting on the H1 and H2 receptors is essential for?
T/F spasticity results from increased gamma-motorneuron activity in the muscle spindle?
Almost all spinal inhibitory reflexes rely on what NT?