The (neuro)vascular system as a key brain-body interface

Question 1

What is the wider aim of systems neuroscience and neuroscience more generally?

Answer 1

To deliver answers about how the brain works

Question 2

What is an important idea for systems of brain and body?

Answer 2

That the brain is embodied in the body but that it is also embodied in the self too

Question 3

The connection of the CNS to the wider world is usually simplified as what?

Answer 3

Sensory input and motor output (behaviour)

The wider world is releveant to motor output and to sensory input

Question 4

This connection to the wider world is implemented by what?

Answer 4

The peripheral nervous system

Question 5

What is the peripheral nervious system (PNS)?

Answer 5

The peripheral nervous system consists of the nerves that branch out from the brain and spinal cord – these nerves form the communication network between the CNS and the body parts

PNS enables the nervous system to reach into the body for both sensation and control

Actions can be specific (e.g. modulation of a reflex) and generic (e.g. fight or flight responses)

Question 6

What are the two main subdivisions of the PNS?

Answer 6

Sensory (afferent) division
-composed of sensory neurons
-conducts signals from receptors to CNS

Motor (efferent) division
-composed of motor neurons
-conducts signals from CNS to effectors

Question 7

What is the motor division further subdivided into?

Answer 7

Autonomic nervous system
-controls involuntary responses

Somatic nervous system
-controls voluntary movement

Question 8

What is the autonomic nervous system further divided into?

Answer 8

Sympathetic division
-mobilises body systems
-fight or flight responses

Parasympathetic division
-conserves energy
-rest and digest responses

Question 9

What two things are also considered a key route for body communication aside from the nervous system?

Answer 9

The vascular system
Blood-brain-barrier

Question 10

Why is communication through the vascular system and BBB important?

Answer 10

Because this form of communication is often important in the context of health and disease

Question 11

How does brain mass correlate with cardiac output?

Answer 11

Brain is 2% of body mass but demands 20% of cardiac output

Constantly using high amounts of energy, demanding organ which is costly to maintain

Question 12

What does limited storage capacity in the brain mean?

Answer 12

No local storage capacity in the brain, with very little reserves, especially oxygen

This means that the brain needs an excellent supply chain especially because interruption of blood supply for just a few seconds can cause local and/or global injury

This is also important given that there is only about 50um (microns) between capilaries so each neuron effectively has its own supply capillary

This means that in cardiovascular disease you don’t need a lot of the disease to start impairing the ability of neurons to function- we need smart supply logistics

Question 13

How do we manage blood supply with changing demands?

Answer 13

Neurovascular coupling

Question 14

What is NVC?

Answer 14

Neurovascular coupling refers to the mechanism that links the transient neural activity to the subsequent change in cerebral blood flow

The magnitude and spatial location of blood flow changes are tightly linked to changes in neural activity through a complex sequence of coordinated events involving neurons, glia, and vascular cells.

Many vascular-based functional brain imaging techniques, such as fMRI, rely on this coupling to infer changes in neural activity.

Question 15

What is an important part of the NVU?

Answer 15

The BBB

Question 16

What is the BBB?

Answer 16

Interconnected system of neurons, astrocytes, pericytes and vascular cells (endothelial cells in particular) whihc provide the blood-brain barrier

The BBB shields the brain from toxic substances in the blood, supplies brain tissues with nutrients, and filters harmful compounds from the brain back to the bloodstream

BBB underpins neurovascular function and neurovascular coupling

Question 17

What are the three main transports across the BBB?

Answer 17

1. Diffusion- Only water, glucose, certain gases (e.g. oxygen), and lipid-soluble substances can easily diffuse across the barrier
2. Special transport proteins- at the BBB, multiple uptake transporters are responsible for bringing solutes from circulation into the endothelial cells and then into the brain across the basolateral membrane.
3. Transcytosis- the vesicular transport of macromolecules from one side of a cell to the other

Question 18

Why is it hard to design drugs for the CNS?

Answer 18

Difficult to develop drugs that can cross the BBB

Question 19

How is the vascular system more than plumbing?

Answer 19

It’s a complex, active control system at the gateway of brain-body and body-brain interactions

Question 20

What does Hormones and Behaviour (McEwen, 2019) illustate?

Answer 20

Illustrates interactivity of brain and body via hormones, with a focus on stress responses and plasticity

Question 21

What is oxytocin?

Answer 21

Fundamentally it’s a signalling molecule that is transported between the organs of the body by the vascular system

Oxytocin can induce anti-stress-like effects such as reduction of blood pressure and cortisol levels

Question 22

What is a hormone?

Answer 22

A signalling molecule that is transported between organs of the body by the vascular system

Hormones are essential for the regulation of development, physiology and behaviour
–Many jobs involve more than one hormone e.g. oxytocin is involved broadly in bonding and reproduction but within that its doing other things important for bonding for infant and mother, relevant to production of milk and in relationships

They are produced by many organs of the body (the endocrine system), with receptors similarly located in many places, hormones can be detected nearly anywhere in the body

Question 23

What is the principle function of hormones?

Answer 23

Aside from signalling, their main function is REGULATION, hormones keep you in a zone that is adaptive to the internal and external environment in which you are in

Question 24

Give a good example that shows the function of hormones as a regulator.

Answer 24

Temperature- there is often a set point, when youre well is about 37 degrees, but error in set point can be fed back with a feedback control system
similar to central heating in homes – to enact some change with the intention of restoring that value of body temperature back towards that set point

The set point can vary, e.g. if you’re unwell the set point can be elevated, its adaptive in a sense that it can help to combat the infection to clear the pathogen

Question 25

What do hormones, along with neurotransmitters underpin?

Answer 25

Signalling within brain-body systems that act to maintain a desired set point in terms of behaviour or physiology

Question 26

What can the term ‘set point’ be better replaced with?

Answer 26

‘Desired state’ – as set point can be quite transient and itself dependent on input from other brain and body control systems

Question 27

Are hormones under control of the brain?

Answer 27

Under some level of ‘master control’ by the brain, although this is itself set within a complex feedback architecture thus undermining the concept of a control hierarchy

Question 28

Describe how there is master control of hormones from the brain.

Answer 28

There is some master control of hormones in the brain, particualrly the hypothalamus

The hypothalamus is a receiver through hormones and other signalling of the nervous system, but you could argue that the hypothalamus itself it is a subject of higher order levels of control e.g. stress, the hypothalmus drives a bodily feeling of stress but in a funny way it could be your capacity to think about something really scary that can drive that stress response, so the hypothalamus is just responding to cognitions that you might have

So this feedback architectures that make neat hierarchies hard to pin down

Question 29

What is the endocrine system?

Answer 29

Effectively a set of glands within, or aligned with, things in the body

It is the glands and organs that make hormones and release them directly into the blood so they can travel to tissues and organs all over the body. The hormones released by the endocrine system control many important functions in the body, including growth and development, metabolism, and reproduction.

Most of the glands are not in the brain, other than hypothalamus and pituitary (sort of in the brain)

Question 30

How are hormones and neurotransmitters different in terms of action onset?

Answer 30

NTs - fast acting (onset)
Hormones - slow acting (onset)

so theres a slower action of hormones but they can travel further distances compared to NTs

Question 31

How are hormones and neurotransmitters different in terms of travel?

Answer 31

NTs are restricted to nerve pathways but hormones can travel anywhere via circulatory system, means that they can essentially access any tissue in the body

Question 32

How are hormones and neurotransmitters different in terms of duration of action?

Answer 32

NTs tend to have short durations of action whereas hormones have long duration of action

There is some overlap there e.g. there can be certain NT states and changes in NT levels which can operate over the course of years e.g. mental illnesses may invovles changes in NT functionality but generally they have a short duration of action

Question 33

How are hormones and neurotransmitters different in terms of digital vs analogue action?

Answer 33

NTs becuase they’re goverened by neuronal signalling tend to be a bit more digital in action because they’re fundamentally linked to the digital signalling of neurons, however, its not quite as simple as that because we know the rate of firing will relate to the volume of NT release and spatial and temporal summation, so its not totally digital but being connected to neurons does make it quite digital

Hormones are much more analogue (continuously variable)
e.g. hormonal changes that relate to sexual development, the development of secondary sex characteristics, they can start from very low levels and move up to very hihg levels over a very large dynamic range with analogue action whihc is more relevant to this kind of system

Question 34

How are hormones and neurotransmitters different in terms of targeted vs diffuse actions?

Answer 34

NTs tend to have more targetted action within specific networks of the brain e.g. nigra-striatal dopamine pathway in parkinsons

Hormones tend to have more diffuse action- because its carried by the circulatory system which goes everywehre, horomes are almost always going to be going everywhere and affecting a wide range of tissues

Question 35

Summarise the overall differences between hormones and NTs.

Answer 35

Hormones are thus able to not only access parts of us that neurotransmitters cannot reach, but are also able to offer a qualitatively different mechanism of signalling that may complement that orchestrated by the CNS/PNS

We can think of hormones and the hormone highway through the vascular system as being a bit like a nervous system in terms of the way it reaches into tissue, it signals, its relevant over different time scales, but it operates with a different set of parameters, it does a lot of things that neural systems cannot easily do because of evolution

Question 36

How does the hormone highway work?

Answer 36

Secreting cell- secretes a hormone within an endocrine gland , travels along the blood stream, will diffuse out in different places but at some point it will diffuse out and hit the target cell receptor

in the same way NTs work in that lock & key way, similar thing occurs with hormones
- though hormones are released everywhere, the selectivity comes about because only certain tissues will have target cells that are sensitive to that particular hormone

Question 37

Hormones act on what?

Answer 37

Hormones can travel into and out of the brain

They can act on themselves but in some ways they can also act on the BBB

They regulate the movement of hormones between the body and the brain as well as regulatory feedback

Question 38

What is the hypothalamus considered to be?

Answer 38

A master controller

Question 39

What two pieces of information does the hypothalamus receive?

Answer 39

1. Contextual information- things the cortex knows about - where are you in space, olfactory space, visual space
   -Also get key contextual information which is more internal from the amygdala invovled in emotion that feeds into the hypothalamus so it has an affective emotional space and context
   -Also context from the hippocampal formation, connected to the limbic system is also related to emotion and memory
2. Sensory information - key internal sensory information, visceral and somatic sensory pathways, chemosensory and humoural signals e.g. the salt balance in blood related to osmoregulation, hunger, temperature, internal body sensing

Question 40

What does having contextual information and sensory information mean for the hypothalamus?

Answer 40

The hypothalamus knows about the status of the body and has a lot of contextual information which helps it to know what your set point needs to be in a particular context so that it can connect to different effectors
e.g. make you shiver if cold, motivation to seek food, curl up and retreat if injured

This information makes it a hub of relevant information that can set the conditions for the behaviours that you need in order to do that

Question 41

Does the hypothalamus seem to be a master controller? Thinking beings

Answer 41

Understanding the top of the control hierarchy is still complicated esepcially because we as humans are thinking beings
e.g. we can think about theoretical or dark things and work outselves into very stressgul states- this cortical information is actually driving some of these feelings in the body that get fed into the hypothalamus
This is unlike many animals who, as far as we know, don’t have the capacity to do this

So it can be hard to know what’s in control in this sense

Question 42

Why are techniques like mindfulness prevalent in reducing stress?

Answer 42

These techniques are about exerting a level of control over the hypothalamus and the stress responses that can come from cotrical input- so in this way you can be in charge of your hypothalamus perhaps or you can at least have some leverage with these techniques that many of us use

Question 43

What are the two parts to the pituitary gland?

Answer 43

The anterior pituitary
The posterior pituitary

each one is responsible for a different set of hormones

Question 44

Describe the anterior pituitary hormones.

Answer 44

These are released with a two step process

The hormone doesn’t directly get released from the pituitary, there needs to be a releasing hormone that causes the release of the actual pituitary hormone

Question 45

Give an example of anterior pituitary hormones.
-FSH

Answer 45

Releasing hormone= Gonadotrophin-releasing hormone (GnRH)

Pituitary hormone= Folicle-stimulating hormone (FSH)

Target = Reproductive system

Effects= Stimukates production of sperm and eggs

Question 46

Describe the posterior pituitary hormone.

Answer 46

Has a direct release

The two main hormones are antidiuretic hormone and oxytocin hormone

Question 47

Give an example of a pituitary hormone
-OT

Answer 47

Pituitary hormone= Oxytocin

Target= Female reproductive system

Effects= Triggers uterine contractions during childbirth

Question 48

What is the mechanism of release for anterior pituitary hormones?

Answer 48

AP has a dense network of blood vessels that have the capacity to take on hormones, its ready to have the hormones cross over the BBB into the vascular network

For the AP we have a releasing hormone (e.g. GnRH) that initially releases the hormone into a little branch vascular network which takes it a short distance to the endocrine cells of the anterior pituitary and then that releases further pituitary hormones (e.g. FSH) into the wider blood stream

Question 49

What is the mechanism of release for posterior pituitary hormones?

Answer 49

Cells that originate in hypothalamus, project into the posterior pituitary and then get released into the blood stream

Question 50

The release of all hormones is done by what?

Answer 50

The vascular network

Question 51

What do hormones do?

Answer 51

Regulate physiology in accordance with motivational states e.g. arousal, fear, hunger

Regulate many processes e.g. digestion, metabolism, respiration, tissue function, sensory perception, sleep, excretion, lactation, growth and development, movement, reproduction.

Question 52

What are the common processes of hormones?

Answer 52

Feedforward and feedback signalling, bidirectional influences between body and brain.

Question 53

What is an example of the complexity of hormone regulation?

Answer 53

The menstrual cycle

Several different hormones having a complex cycle of changes in release, in the concentration of that release over the course of approx. 1 month

It’s a complex system- each of the different components is important for different parts of physiology and the timing is all interlinked

Question 54

What is the consequence of having a dysfunctional or distracted vascular system?

Answer 54

Impairs the ability of the hormone highway, the vascular system to get effectively to all of the tissues of the body

Dysfucntional- narrowing or damage to blood vessels or endothelial cells e.g. cardiovascular disease

Distracted- referring to immune systems and immune responses- in an immune response situation, the endothelial cells and cells relevant to neurovascular BBB actaully change into a different mode of operation, they’re distracted from normal gatekeeping and regulation of BBB