Physiology & Anatomy 2

LTP is a process by which synaptic connections between neurons become stronger with frequent activation. It is thought to be a way in which the brain changes in response to experience and thus may be a mechanism underlying learing and memory. 

LTD is a process by which synaptic connections between neurons are weakend. It may be important for memory formation → by resetting previous synaptic changes to allow for new memories to be formed via long-term potentation (LTP) 

The bilateral removal of the hippocampal formation and allied structures in H.M. had important implications for the understanding of the neurobiological basis of learning and memory: 

1. It supports the theory of different forms of memory: short term vs long term
2. It indicates that the temporal lobe, is a critical neuronal substrate necessary for specific forms of learning and memory
3. Hippocampus is not the ultimate structure for long-term storage of declaratice memories
4. Medial temporal lobe structures are important for the formation of new memories 

• In response to conditions of acute energy deficiency or chronic energy deficiency the brain initiates behavioral, autonomuc and neuroendocrine response to increase availability of fuel to the CNS
• Response may be: Increase in feeding an hepatic glucose production, in parallel the body conserves energy by inhibiting growth and reproduction while reducing metabolic rate through the suppression of the HPT axis 

• Stress activated both anorexigenix and orexigenic pathways
• Balance between the pathways shift to anorexigenic if high calorie food is not available, and shifts to orexigenix if high calorie food is available 
• Both is possible: People that eat less in stressful times and people that eat more in stressful times 

• Failure to produce leptin would result in obesity
• Low leptin secretion for a given fat mass. The fat mass would expand until normal leptin levels are reached, resulting in obesity 
• Obesity could result from insensitivity to leptin at its site of action 

1. Preoccupation/anticipation phase: Where there is exaggerated motivation fo drug use
2. Binge / intoxication phase: Characterized by the downregulation of positive responses and a subsequent increase in the level of drug intake → dose needs to be increased to get the positive effect
3. Withdrawl: Negative effect phase where addictive substances become the driving force for contiues drug seeking and intake 

• Drug self-administraton: Availablinity play a role in determining the pattern of druf intake
• Restriction of drug access a few hours a day produces a regular and stable pattern of consumption 
• Escalation of drug intake may set the stage for addiction 

• Weight gain, DA response becomes insensitive
• Leads to overeating which leads to even lower DA response
• People at high risks for obesity have a hypersensitive DA respnse 
• Additional factors: Stress, poor nutrition, genetics, environmental toxins 

Healthy axons sprout nre nerve endings that connect to other pathways in the CNS

Could be used to strengthen existing conncections ot the repair damaged parts of the CNS by repairing damaged pathways

Synapses start to form around the \(36^{th}\)week of gestation and it gets denser for about 2 years, converging to a fully connected neural network

After it gets as dense as it possibly can, some synapses that do not conduct action potential on a frequent basis starts to disappeat and the number of connections start to decline

As we age, old connections are deleted

Synaptic pruning eliminates weaker synaptic contracts while stronger connections are kept and strengthend 

• Retrograde amnesia: event for a period of time before the traume are forgotten, but memories from the distant past and the period following (future) are in tact
• Anterograde amnesia: Events before the trauma can be remembered but there are no memories for the period following the trauma 

The bilateral removal of the hippocampal formation and allied structures in H.M has important implications fro the understanding of the neurobiological basis of learning and memory

• It supports the theory of different forms of memory: Short and long term
• It indicates that the temporal lobe is a critical neuronal substrate necessary for specific forms of learning and memory (declarative)
• The hippocampus is not the ultimate structure for long-term storage of declarative memories 
• Medial temporal lobe structures are important for the formation of new (declarative) memories, which are then imprinted on the other brain structures

• With age it becomes harder to ignore irrelevant information
• It also becomes harder to switch between tasks with different requirements
• These difficulties can make it more difficult to hold relevant information in mind and switch between different task requirements 

Characteristics of brain aging is loss of brain volume (white matter > gray matter) especially in the hippocampus and frontal lobes → loss of myelin, synpases and dendritic arbor, cystoskeletabl changes (accumulation of neurofibrilarry tangles and deposition of amyloids in the brain and blood vessels) 

Aging is associated with progressive losses in function across multiple systems (sensation, cognition, memory, motor control and affect) and they occur with increasing age. 

• Maintenance or improvement of cognitive performance
• Larger brain and hippocampal volumes were associated with preserved cognitive function
• Ability to make decisions and remain independent
• Avoidance of disease and disability by maintenance of physical, cognitive and sustained social engagement 

• Chronic neurodegenerative disorder
• Progressive dementia (= group of symptoms affecting thinking and social abilities) 
• Loss of memory
• Cognitive decline
• Changes in personality 

• Depending on activities there is more or less blood flow through certain body parts: When doing sports → blood supply to skeletal muscle increases, blood supply to kindeys/ gut system decreases 
• When resting: Blood supply to skeletal muscle decreases 

• Common mental disorder 
• Leading cause of disability world wide and is a major contributor to the overall global burden of disease
• More women affected by depression than med
• There are psychological and pharmacological treatments for depression 

• The most important genetic risk factor for AD is the apoE4 gene
• ApoE4 is one of three variants of the apoE gene
• If a person carries the apoE4 (for one parent) --> three times the risk to develop AD
• If a person carries 2 apoE4 genes the risk increases to ten times 

• Is the membrane enclosing the heart, the heart floats in fluid inside pericardium
• Prevents overstretching
• Reduces friction during contractions

• It generates its own beating and doesnt need nerves to beat 
• However the heart beat rate is controlled by nerves (autonomic nerves system)

The heart is a pump. Pumps blood from body to lungs and back to body (circulation cycle). While passing through lungs, the blood acquires oxygen and gets rid of CO₂ (which were used up and produced by body metabolism)

For a heart muscle cell to contract, a membrane potential is required. The ultimate contraction is Ca2+ concentration dependent. (voltage gated Ca2+ channels → calcium increase causes force)

blue controls green

green controla red

An isolated heart without calcium will stop beating, with calcium the beating will continue 

In muscle cells, there are actin and myosin fibres inside. Myosin paddles along actin in an ATP-dependent manner. This sliding of actin and myosin relative of each other = contraction. 

Myosin can only bind to actin (and thus do contractions) when the calcium concentration is high. 

The Ca²⁺ for the contractoin comes from the extracellular space and from sarcoplasmic reticulum

1. Depolarization of the muscle cell membrane (caused from neurotransmission) leads to opening of the \(Ca^{2+}\)voltage gated ion channels
2. \(Ca^{2+}\)ions flow in (\(Ca^{2+}\)usually high outside and low inside the cell), \(Ca^{2+}\)binding to sarcoplasmatic reticulu also causes \(Ca^{2+}\) storage to flow out ⇒\(Ca^{2+}\)concentration gets even higher
3. \(Ca^{2+}\)act on myosin / actin → contraction 

• Voltage gates Ion channels: activated in certain ranges of membrane voltage. 
• Current through these channels changes membrane voltage
• So voltage-gated channels influence each others gating / opening by influencing voltage

This and different activation speeds of different channels (Na⁺ fast, K⁺ slow), produce self-sustaning cycling/oscillations in membrane voltage --> pacemaking 

Because heart cells generate electrical waves roughly in sync with eachother, the combined waves of electricity are large enough to be recorded from the outside of patient's chest. This enables physicians to record ECG, from which they can look at rhythm abnormalities etc. 

A graph of voltage versus time of the electrical activity of the heart using electrodes placed on the skin. These electrodes detect the small electrical changes that are a conseqeunce of cardiac muscle depolarization followed by repolarization during each cardiac cycle. 

• Heart cells are connected to each other mechanically and electrically (syncytium) 
• This is an essential feature that enables the heart to work. Otherwise each cell would beat in isolation and there will be no overall contraction of the pump 

• Electrical = gap junction proteins
• Mechanical = desmosome proteins 

Eletromechanical coupling between heart cells produces coordinated contraction of the whole heart. This is critical for blood pumping 

The heart cells that set/entrain the whole heart are located in the sino-atrial node (SAN- in right atrium wall)

SAN = natrual pacemaker of the heart

The rate is transferred through all cells via electrical connection

Heart valves ensure one way flow of blood. This is necesary for sending blood flow in the correct direction during contractions of atria and ventricles. 

1. Atrio-Ventricular Valces: prevent blood from flowing from ventricles to atria
2. Semilunar valves: Prevent the return of blood to the heart

The heart beats autonomously (self-generated). The rate of this beat is modulated by autonomic motor nerves (ACh, NA) 

Sympathetic nerve activity --> releases NA on heart --> accelerates heart rate

Parasympathetic nerve activity --> releases ACh on heart --> slows down heart rate 

FS mechanism: the more blood enters the heart, the stronger the heart contracts (intrinsic regulation of heart pumping)

Coronary arteries supply heart with blood. Their clogging leads to heart attack (damage to heart muscles)

There are 2 key functions a heart has to deal with in order to work properly and supply the body with nutrients and oxygen: amount of workload (amount of blood) and contractility (ability to contract in the way it should). Therefor heart failure has to do with either one of those or both of these factors

 = Output insufficient to provide enough O₂ for tissue

• Classic heart-force-increasing agents 
• Cardiac glycoside drugs increase force by increasing cytosolic Ca²⁺
• Cardiac glycoside drugs: Block Na/K pump. This makes more Calcium enter intracellular Ca²⁺ stores. So stronger contraction during electrical stimulation

1. Block Na⁺ pump, so Na⁺ goes up
2. Less Ca²⁺ leaves via Na⁺/Ca²⁺ exchanger
3. More Ca²⁺ into SR
4. More Ca²⁺ release!

Block blood vessel adaptations (constriction) that are normally caused by reduced cardiac output. This prevents failing heart from being destroyed further by its work load 

It makes blood pressure decrease and therefore work load decrease, so that the failing heart can still pump without getting too stressed