BME365R

Neuro-Physiology Homework 2017

Note: HW must be submitted by noon of the day indicated to receive full credit

HW 8: due 11-7. Feedback control, hypothalamus, and memory

The control circuit for an artificial knee is shown in the diagram below:

Assume that G(s)=1/[ (s+100)] and K=106.

(a) What is the approximate closed-loop gain function? Gc=θo/θi

(b) Draw the Bode Plot of both the closed loop gain function and the open loop gain
function.

(c) What conclusions can you make by comparing the two Bode plots?

The closed loop function has a lower gain than the open loop, but both plots have the
same frequency response.

(d) What advantage does the closed loop gain function have?

The closed loop gain function has the advantage that it is able to achieve the same
frequency response with less gain.

(e) Assume G(s)=1 and H(s)=1/10. How large must K be to ensure that a 1% change in K
results in only a 0.01% change in closed loop gain?

(f) What are some physiological examples of closed-loop control in the CNS?
Closed-loop control in the CNS involves the use of feedback and error
detection/correction to maintain the desired state. During the course of an action,
feedback is compared against a standard to enable an action to be carried out as planned.
Information about ongoing movement is used to update and alter the original motor
commands sent by CNS. This describes controlled adjustments based on detected sensory
information. The movements are modified at spinal and brainstem levels. Examples of
this are vision and somatosensory feedback.
(g) List one example of positive feedback in the CNS.

An example of positive feedback in the CNS is an action potential. Depolarization

triggers the rapid opening of sodium ion channel gates, and the slow opening of
potassium ion channels. Sodium rapidly enters the cell, resulting in more depolarization,
and the continued rapid opening of the sodium ion channel gates. This is a positive
feedback loop.

(h) What parts of your brain regulate sleep?

The temporal area of the brain, specifically the reticular activating system and the pons,
regulate sleep. The reticular activating system is involved in arousal, attention, sleep and
wakefulness, and controls the reflexes. The pons also regulates states of arousal,
specifically in sleep and dreaming.

(i)Why do we sleep?

Sleep can be characterized as REM sleep (rapid eye movement), during which the brain
activity inhibits motor neurons to skeletal muscles, and slow-wave deep sleep (non-
REM). Deep sleep is needed to repair free radical damage to membranes. REM sleep,
during which most dreaming occurs, is important for learning and memory. Post-synaptic
receptors are renormalized to full sensitivity, and synaptic homeostasis is reset. This
functions to remove unimportant memory traces that have formed as neurons that get
activated together strengthen their links. Sleep returns these synapses to a baseline level
of strength, maintaining synaptic homeostasis.

(j) Read and critique the articles:

Luisa de Vivo, et. al. Ultrastructural evidence for synaptic scaling across the wake/sleep
cycle, Science, 355:6324, 3 Feb 2017, 507-510.

This article examines the hypothesis that a principal function of sleep is to renormalize
the overall synaptic strength that is increased when awake. The researchers used 3D-
electron microscopy to measure synapses in mouse motor and sensory cortices. They
measured the decrease in the axon-spine interface (ASI) after sleep as compared to during
wake, and found that the decrease was proportional to ASI size. This introduced the
concept of scaling. This article highlights that the scaling of synaptic size varies and is
not uniform because learning during wake selectively potentiates synapses, and during
sleep there is selective renormalization. This selective renormalization during sleep is
what allows for memory consolidation and forgetting of unnecessary information. The
next steps for further research would be to examine how scaling is distributed across
wake and sleep.

Graham H. Diering, et. al. Homerla drives homeostatic scaling-down of excitatory

synapses during sleep, Science, 355:6324, 3 Feb 2017, 511-515
This article suggests that the homeostatic scaling-down remodels synapses and
consolidates memory during sleep. The research indicates that this change is compelled
by Homer1a, an immediate early gene that serves as a molecular integrator of arousal and
sleep need. This is done via neuromodulators, noradrenaline and adenosine. The
researchers examined mouse forebrain synapses during light and dark cycles to
understand the synaptic changes during homeostatic scaling-down in vitro. The group
aimed to determine the mechanism controlling the Homer1a synapse targeting, which is
linked with learning and neuronal activity. This was done by sleep-depriving mice. The
results of this research indicated that scaling-down during sleep is “likely under the
control of a coordinated interplay of neuromodulators, such as NA and adenosine,” and
that scaling-up is actually inhibited by sleep. These findings support the idea that scaling
up and down are each controlled by distinct mechanisms. Further research could include
exploring additional mechanisms by which sleep is able to support cognitive function.

What happens to synapses when we sleep and what controls the synaptic modifications?

When we sleep, synaptic strength is weakened and renormalized. When we are awake,
learning occurs through synaptic potentiation. As a result, synaptic strength is increased.
During sleep, we are disconnected from the environment and spontaneous neuronal
activity can comprehensively sample memories. This allows the brain to consolidate new
information and restore cellular function.

(k) How is a memory trace created and how do we recall memories? Are memories stored
in large or small networks of neurons and where are the networks located in the cortex?

Memories are stored throughout the cerebral cortex through memory traces. Brain circuits
may work in parallel through parallel processing to learn and remember things, to help
provide a backup in case one circuit is damaged. A stimulus comes into the CNS and first
goes into short-term memory. With effort to retain that memory, such as repetition of the
information, it is then processed and consolidated into long-term memory. This storage
area can hold vast amounts of information, ready to be recalled and processed as an
output (via speech, action, etc.). Memory relies on the brain’s ability to reuse specific
neurons that eventually elicit these responses. Neurons can become linked when similar
memories reuse the same connections to elicit the same response. The center of memory
and the vast amounts of neurons in the brain is the amygdala.

(l) Read and critique the article about memory linking:

Alcino J. Silva, Memory’s intricate web, Scientific American, 317:1, July, 2017, 30-37.

The research behind this article provides a proof of the CREB gene correlation to
memory. This can lead to the implication that memory loss is derived from a reduced
amount of the CREB gene. Further research into this field could examine how the CREB
gene can be manipulated to be tested in humans rather than mice. This would improve the
efficiency of this gene as a way by which to help human patients with memory loss.

(m) What role does B amyloid and Tau play in Alzheimer’s disease? When does
Alzheimer’s disease pathophysiology begin? Is Alzheimer’s disease a primary neuro-
vascular disease? How can we image the small vessels in the brain in vivo?

Beta amyloid and Tau play a significant role in Alzheimer’s disease. The buildup and
plaque formation interfered with the brain’s functionality, beginning in mid- to late life.
Alzheimer’s disease is a primary neurovascular disease because of its direct correlation to
beta amyloid plaque. We can image small vessels in the brain in vivo using voltage-
sensitive dye imaging.

(n) Read and critique the article:

Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid
Deposition, Rebecca F. Gottesman, MD, PhD; Andrea L. C. Schneider,MD, PhD; Yun
Zhou, PhD; Josef Coresh, MD, PhD; Edward Green, MD; Naresh Gupta, MD; David S.
Knopman, MD; Akiva Mintz, MD; Arman Rahmim, PhD; A. Richey Sharrett,MD,
DrPH; Lynne E.Wagenknecht, DrPH; Dean F.Wong,MD, PhD; Thomas H. Mosley, PhD,
JAMA 317(14), March 2017, 1443-1450.

The research presented in this article indicates that various vascular risk factors in mid-
life are correlated with amyloid buildup in the brain. This suggests that cognition
efficiency is not only linked with the brain, but with the entire body as well. This
increases the complexity and mystery of Alzheimer’s disease. The article sheds light on
these various risk factors, but it does not provide further insight into the potential control
of these risks. Further research into this topic could examine specific means by which
these risk factors can be controlled. While this research would be infinitely vast, this
article provides a starting point and can allow future researchers to narrow their scope
and begin to focus on various prevention methods.