Lecture 2 - Fundamentals of Neurons and Neurotransmission (micro) & Fundamentals of the Central Nervous System

Glial Cells the “Glue”

• Support cells are called Glial

• Glia means glue - originally thought to glue the brain together

Astrocyte

• Serve a variety of functions

• Support blood brain barrier

• Chemical protective systems & barrier that helps protect the introduction of toxins into neurological systems

• Keeps neurotoxic substances out of the brain

• Recovery of brain injury, they release hormones that help respond to that brain injury

• Neurodevelopment - Early versions of this in utero help develop the nervous systems (think of it as the infrastructures down which the new neurons will travel to where they live in the nervous system)

Microglial cells

• Scavengers, eat dead and dying neurons to avoid waste or an electrochemical problem

• Play important role in brain injury to avoid communication problem in brain

Oligodendrocyte & Schwann cells

Both insulate neural signal so it reaches its destination - differ where they occur in the nervous system

Oligodendrocytes

In brain and spinal chord

Schwann

Periphery, arms, legs etc

Neurons

• The primary communicative unit of the nervous system

• Their job is to send information regardless of what that information may be

• 3 Classes differ based on the information they deliver

3 Classes of Neurons

• Motor Neurons

• Sensory Neurons

• Interneurons

Motor Neurons

Trigger movement in the body as appropriate

Sensory Neurons

• Capture sensory info from the environment

• Sight, sound, olfactory, taste etc

• Capture info and send it to the brain for analysis

Interneurons

• Overwhelmingly most of our neurons are this

• Deliver complex info and integrate information across brain regions and within them

• Cog neuro - most challenging thing to understand is to understand how they work and how to decode them bc their functions are more complex

Triggering an Action Potential

• Neuron either sends a signal and activates enough to reach a threshold

• If the threshold is not reached for whatever region, it does not do anything

• All or none principal - a signal is either sent at full power or not at all

• Y axis - membrane potential, models different degrees of input, trying to excite a neuron

• Size of action potential is exactly the same

• More signals represent a more intense stimulus (louder, more painful etc)

Propagation of the Signal down to the Axon

• Axon: long pathway down which a neural signal is sent

• If signal starts near the cell body & the axon hillock summates all the information

• Axon Hillock - have I received enough excitation to send a signal

• Reaches the end or the terminal

• Glial cell that insulates axon - oligodedrocyte

• Why are there gaps between myelin sheath - called nodes of ranvier

  • ‘Electrical gas station’

  • Signal is restored or regenerated

  • If not then it passively fades out

  • Cause another full scale action potential

  • Protects the fidelity of the signal

• Saltatory conduction - as if its jumping from each node of ranvier until it gets to the axon

Myelin Degradation and Neural Failure: Multiple Sclerosis (MS)

• More common in northern altitudes

• 75,000 people diagnosed per year

• Symptoms depend on where the disease starts

• Might start in memory areas or motor areas

• Complex diagnosis bc it doesnt look the same everytime

• Thought that it is an autoimmune disorder

  • When we give people immunosuppressents it mitigates the damage

  • Why? Is there something wrong with the myelin?

• Specifically attacks myelin sheaths, signals do not reach destination, neurons can become dormant & overtime become damaged and die, can see using structural MRIs

• Correlated with low levels of vitamin D

• Central nervous system disorder

Motor Neuron Disease and Neural Failure: Amyotrophic Lateral Sclerosis (ALS)

• Debilitating motor neuron disorder

• Rapidly compromises motor control that control movement from brain to spine and spine to body - complete degradation of motor ability

• First see clumsiness, then walking is taken away, can also take away ability to breath

• In a number of cases is fatal

• Progresses from onset to loss of life from 3-5 years

• Quality of life is impaired dramatically, additionally

• Believe its caused by neurons getting too excited and killing themselves (excitotoxicity) when given medications that reduce neural activity reduces neural death

• Some people can live with a version of ALS for decades

  Ice bucket challenge

Electrical Failure & Neural Failure: Ischemia

• Stroke - interruption of blood supply to part of the body

• When part of body does not get enough blood flow - ischemia

• When neurons cannot get enough oxygen to receive action potential - neural failure

• Ischemia most common type of stroke (more common) - caused by buildup of plaque in arteries, associated with diet, exercise, smoking cigarettes etc

• Brain takes up ¼ of the oxygen we breathe in, profoundly sensitive to this disruption

• 90 minutes into the stroke, neurons can come back to life - if neurons do not receive treatment in time they will die

• Same side of face and body can be affected

• Disruption of speech, drooping face, arm weakness

• Time lost = loss of brain matter

• Treatment - TPA (clot busting agent), Stents (open up blood vessel)

From Electrical to Chemical Transmission

• Once signal gets to end of axon - needs to bridge between neurons

• Chemical is released, bridges neuron A to neuron B

• Reaches terminal, calcium ions reach terminal and come into the neuron and bind to packages of chemicals - vesicles that contain neurochemicals

• Then spill out neurotransmitters into synapse

• Neurotransmitters fit into specific receptors

• This process is crucial for psychopharmacology

• Calcium comes from extracellular fluid

• Calcium does not form a stable 1+ ion

Dopamine

• Synthesized in the brain stem in the substantia nigra - black substance (when you look at a fresh human brain it looks black) and Ventral tegmental area (important for decision making)

• Dopamine crucial role for higher order cognition

  • E.g short term memory

  • Protects quality of our signal so we don't lose our track of thought

• Also controls voluntary movement, one of the areas involved is the basal ganglia

• Reward/reinforcement learning (operant conditioning) - leads to development of addition

• Dysfunction - Parkinson's disease (90% of substantia nigra has died) starves ability to control movement, psychotic thoughts and behaviour (strong association between dopamine & mental health), linked to onsets of addiction

• Dopamine has many different receptive types - challenges with psychoactive receptor types, act on a lot of receptors instead of the one that we need

Norepinephrine

• Produced in the locus coeruleus

• Mental arousal - mentally waking you up

• Cognitive arousal/ attention

• Attention is linked to memory - paying attention helps you remember something

• Mental flexibility - deficits in this can become very rigid and have difficulty changing from one behaviour to the next

• Low levels of norepinephrine is linked to lower mood (more relaxed?)

Serotonin

• Produced in the raphe nucleus

• Heavily linked to mood - low serotonin leads to depressed mood

• Medication that boosts serotonin may help depression

• Atypical levels of serotonin - depression, bipolar disorder, has also been linked to psychotic thoughts and behaviour

Acetylcholine

• Produced in the basal forebrain

• Helps processes sensory info, control of attention - consequently support our memory

• In peripheral nervous system - crucial role in control of movement, releases from motor neurons and releases Ach on muscle fibers and causes them to contract

• Alzheimer's disease - deficit associated with memory, basal forebrain completely degenerate and consequently Ach plummets - may be prescribed with meds to increase Ach

• Myasthenia gravis - Ach is altered in the body and cannot bind to the muscle fibers as easily as it should & causes a grave muscle weakness

The same neurochemicals can be involved in a variety of functions

Depending on where it's found in the brain

The ‘game’ of psychopharmacology

• There is an optimal level of a neurotransmitter

• Yerkes-Dodson curve

  • Falling above or below the amount reduces function

• Psychological disorders - challenge in prescribing meds (use behavioural systems to figure out what is happening in the brain, came come to a preliminary diagnosis) → can scan the brain but is not done diagnostically for psychological disorders

• 1 neurotransmitter can affect others, (increasing dopamine can increase norepinephrine)

• Evolution of a menstrual cycle - how neurotransmitters affect cycle

• What medical doctors do - which medication would help most based on collection of symptoms - may not guess right on first try

• Prescription - observation - refinement

Major Descending motor tracts

• Spinal Chord

• Multiple motor tracts in the brain - biggest is corticospinal tract/ pyramidal tract

• Carries out movements

• One side of the brain controls opposite side of the body

• Crossing is called the medullary pyramids

• Right motor cortex controls movement to left side of body

• Impair movement - rubrospinal can help recover that

• Tectospinal - head and eye movement

• Vestibulospinal - balance

• Reticulospinal - muscle tone (gets body ready for action)

Rubrospinal

Can help repair impaired movement

Tectospinal

Head and eye movement

Vestibulospinal

Balance

Reticulospinal

Muscle tone (gets body ready for action)

Major ascending somatosensory tracts

• Motor information goes from the brain to the body

• 2 Ascending or upward pathways that control aspects of touch

• Medial lemniscal tract

• Lateral spinothalamic tract

• Both terminate in the parietal lobes, help us understand where we are being touched and the nature of that touch

Medial lemniscal tract

• Carries touch information

• Carries proprioceptor information (relative position of muscles) knowing where your body is in space

Lateral spinothalamic tract

Carries pain & temperature information

Spinal Chord

• Ventral vs Dorsal

• Segregated path in spine - can have a motor disability without losing sensory information

Ventral

Motor pathway (movement information)

Dorsal

Somatosensory information

Dermatomes of the Human Body

• Map of body that shows how spinal nerves interface with different parts of body

• Very consistent in people

Brain

• 85-90 billion neurons, 10 times as many glial cells

• Typography of the Brain

• Cerebral Cortex and White Matter tracts

• Medial parts of the brain are made up of connections going to different parts of the brain

Typography of the Brain

• See a wrinkly bag - cerebral cortex

• Bulges out and grooves dip

• Bulges - gyrus/gyri

• Groove - sulcus/sulci

Cerebral Cortex and White Matter tracts

• White matter - myelinated axons - pathways going somewhere in the brain

• Outer rim of cortex - grey matter - cell bodies

DTI

Only looks at white matter connections of the brain - tracts neurodevelopment, understanding brain injury & connections have been injured

Inter-individual cortical variability

• Sometimes best guess is what the average brain looks like

• Want to take knowledge brains that were studying and generalizing it for all people

• Challenge in averaging people - trying to draw common knowledge of the brain

The Four Lobes of the Cerebral Cortex

(FPOT)

• Frontal Lobe

• Parietal Lobe

• Occipital Lobe

• Temporal Lobe

Frontal Lobe

• Higher order cognition - control of behaviour, decision making, advanced mental functions

• Control Movement - start of the motor pathway corticospinal tract starts in frontal lobe

• Language production (special part of motor control)

• Brocas Aphasia

Parietal Lobe

• Attention

• Touch cortex/ somatosensory cortex within parietal lobe that contains a map of the body to discern where touch occurs on the body

Occipital Lobe

• Visual processing

• Damage can cause blindness, loss of colour discretion

Temporal Lobe

• Memory, representation or storage of memories (not the only area of the brain that has memory functions)

• Dramatic impairments are caused due to Temporal Lobe

• Alzheimer's disease

• Audition

• Language comprehension

• Wernicke's Aphasia/Area

Primary sensory and motor cortex

• Areas of the brain that only processes 1 type of sense

• Every sense has a primary area in the brain and only process 1 sense

• Secondary sensory or motor cortex - still prioritize 1 sense

• Association cortex - thoughts, ideas, decisions, memories (most of the brain)

  • Processes 2 or more senses at the same time

  • Damage to these areas create complex symptoms

• Frontal & temporal lobe is mostly association

• Parietal lobe - mostly association cortex

Association cortex

• Thoughts, ideas, decisions, memories (most of the brain)

• Processes 2 or more senses at the same time

• Damage to these areas create complex symptoms

Superior/dorsal

Higher or above

Inferior/ ventral

Lower or below

Anterior/ rostral

Front of the brain

Posterior / caudal

Back of brain

Medial

Towards middle of the brain

Lateral

Towards outside of brain

Planes of View: Sagittal

• 3 different ways we can look at the brain

• Profile view - sliced along the middle

Planes of View: Axial/ horizontal

• Most common in cognitive neuroscience

• Birds eye view

• Can see both sides of the brain at the same time, sometimes when you think about something you use 1 side of the brain than the other

• If one side of brain is damaged, the other side is the best guess for what it should've looked like

Planes of View: Coronal

Head on view

Topographic Correspondence

• Motor cortex - frontal lobe

• Somatosensory cortex - parietal lobe

• Face and hands gets the most space in the motor cortex

• Allows for excellent motor control over hands and facial expressions

• Somatosensory cortex - more pain and touch preceptors

• Wilder Penfield mapped each of these cortexes

• Need to know only functional implications

Alzheimer's

• Norepinephrine levels decrease

• Affect attention and memory

• Linked to reductions or impairments in consciousness (patients can forget who they are or who they're talking to)

The lymbic system is

involved in emotion and memory

Amygdala

A crucial role in the processing of emotion (almond shaped structure) and at the end of the hippocampus

Hippocampus

Crucial role in new conscious or declarative memories

Corpus callosum

• Band of white matter or myelinated axons that connect the white side of the brain to the right

• Was cut in history - done to reduce the severity of seizures

Thalamus

• Large nucleus one the left side and the right side - sensory relay station - every sensation except smell synapses on the thalamus before going to other areas to process the information

• Crucial role in consciousness - damage to the thalamus can result in profound impairments of consciousness

Basal Ganglia

consists of three parts - very important for procedural learning, different motor acts (shooting a basketball, riding a bike etc), plays an important role for habits (things we do on autopilot) - skills we don’t need to focus much mental energy on

Basal Ganglia’s three parts

• Caudate nucleus 

• Putamen

• Globus pallidus

Cerebellum

Small cauliflower shaped structure at the back of the brain - used to think the primary function was coordination of movement - cerebellum plays a role in smoothing out the move and executing it accurate - people who have damage to it have difficulty in the control of movement (reaching for objects, the ability to walk, moving etc) - linked to many different cognitive functions such as language and memory, executive functions and cognitive control

Ventricular System

• Protect the brain

• Inside the brain cavity - there are chambers of fluid - ventricles - 4 chambers that make up the ventricular system - also connected to the fluid system in the spine - if there is bleeding in the brain, that blood would also be found in the spine, we could draw blood from the spine to get a sense of the integrity of the nervous system - can detect bleeds and infections (ex. meningitis) - typically the fluid is clear but if there is blood in it then something is wrong

• Also helps eliminate waste from the nervous system

Lateral (side) ventricles

Have one that runs from front to back in each hemisphere

Third ventricle

Connected to the lateral ventricles - located in the middle of the brain

Fourth ventricle

Connected to third ventricle - supplies the cerebellum and the brainstem (connection to the fluid system in the spine)

Reason why there is fluid and not more brain

Helps the integrity of the brain - to keep the brain in the same space and not moving around violently - chambers of fluid allow us to move our heads violently from side to side without creating any issues

The Brains Power Supply: Cerebral Vasculature

• Blood flow that is rich with oxygen is required for the brain - the lungs send up oxygenated blood through the carotid artery and the vertebral artery - going north straight to your brain

• Ensure that an adequate amount of glucose and oxygen are provided to these various areas of the cortex so thinking can operate as intended

Carotid artery

Runs through the neck

Vertebral artery

Runs through the vertebrae

All these arteries come together at the bottom of the brain at a structure called

the circle of Willis - from the circle of willis - three major arteries go out to the cortex

Three major arteries that go out to the cortex

• Anterior cerebral artery (front)

• Posterior cerebral artery (back)

• Middle cerebral artery

Anterior cerebral artery (front)

Along the middle lines (medial aspects) - covers the frontal lobe and the middle part of the parietal lobe

Posterior cerebral artery (back)

Pofuses the occipital cortex and the inferior (ventral) parts of the temporal lobe here

Middle cerebral artery

Plays a role in covering the lateral surface of our brain and the bottom - covers a massive amount of brain - many neuropsychological conditions that are caused occur in the middle cerebral artery distribution