IMED1004 - How the brain works (L19)

Revision of Neuroanatomy

DIAGRAM ON SLIDE 3

What your brain already knows about your brain

ON?

- Ligand binds receptor on postsynaptic neuron

- ion channel or cell signal

.

OFF?

- enzymatic breakdown

- reuptake of presynpatic neuron

Neurotransmitters and Synaptic Transmission

A neurotransmitter can lead to synpatic transmission that is: Excitatory OR Inhibitory OR either

The post synpatic membrane may respond via:

- Ion Channels (e.g glutamate and GABA) OR

- Transmembrane proteins that signal secondary messenger systems such as cAMP via G-protein coupled receptors (GCPRs) (e.g monoamines i.e noradrenaline, dopamine, serotonin)

Neurotransmitters (NTs) removal

ENZYME DEGREDATION:

- neurotransmitter broken into fragments (e.g monoamine oxidase (MAO))

REUPTAKE:

- NT/broken products reabsorbed by transport proteins

DIFFUSION:

- Simple diffusion away from synapse. In CNS astrocytes absorb and return NT to presynpatic Neuron

Sensory Input

- GENERAL SENSORY INFORMATION:

- e.g Dorsal Column Medial Lemniscus (DCML) Tract (carries discriminative touch), OR spinocerebellar tract (proprioception)

General Sensory Information

e.g Dorsal Column Medial Lemniscus (DCML) Tract (carries discriminative touch)

.

- dorsal column is telling you that it is the sensory pathway, it is moving up on the dorsal part of the spinal cord

- Medial Lemniscus is telling you that the cross over of that tract is happening within the brainstem, which is where the medial meniscus is

Brain Part

- we are coming back to the central sulcus

- in blue

.

- information where sensation comes from is the first somatic sensory area

- central sulcus lies between regions 4 (red) and 3 (blue)

- when you want to produce a motor command (the intiiation for the actual command) comes from the primary motor area (red) (pre-central gyrus)

- then its going to descend (next slide)

Motor Output

- the command is going to descend (from prev slide) out the black pathway to the muscle)

Motor Output with info

- e.g via the Lateral and Anterior Corticospinal Tract (voluntary movement of limbs)

.

- starts in pre-central gyrus (primary motor area)

- descend through midbrain

- cross at one point or the other, either at the midbrain or at thre level of the spinal cord then its going to reach the muscle on the other side

- left brain controls right side

All we need for this on/off is

neurotransmitters

- Glutamate, GABA, ACh will do that (ionotropic)

But CNS is not just a sensory and motor, theres also a bunch of other stuff

DIAGRAM ON SLIDE 15

The Limbic System

- the mammilian brain for: emotions, memories, habits, attachments

- if we go back down our longitudinal fissure that separates the hemispheres, we have this cingulate gyrus

- thats at the base of the longitudinal tissue on the left and right hand sides

- so we have this little gyrus at the bottom

The two biggies (CNS)

GLUTAMATE:

- The dominant excitatory CNS neurotransmitter

- binds/opens iGluRs (ionotropic glutamtae receptors)

- AMPA receptor is a Na+ channel (EPSP)

- NMDA receptor is a Na+ and Ca2+ channel (EPSP)

- Also mGluRs (metabotropic glutamate receptors)

.

GABA

- the dominant inhibitory CNS neurotransmitter

Binds/opens GABA(A)Rs: Cl- channels:

- Cl- influx causing hyperpolarisation

- inhibits post-synaptic neuron (IPSP)

.

- also GABA(B)Rs: metabotropic

The two biggies (PNS - also in CNS)

ACETYLCHOLINE (ACh) - excitatory or inhibitory:

Nicotinic (nAChR)

- Ionotropic - ligand-gated Na+ channel

- always excitatory

Muscarinic (mAChR) - GPCRs

- metabotropic - activates enzymes

- often inhibitory (can be excitatory)

.

NORADRENALINE (NA) - excitatory or inhibitory

Alpha-adrenergic receptors - GPCRs

- metabotropic - activates enzymes

- excitatory or inhibitory

Beta-adrenergic receptors - GPCRs

- metabotropic - activates enzymes

- excitatory or inhibitory

Glutamate = and GABA =

- Glutamte: excitatory

- GABA: inhibitory

Glutamate

- diagram shows that if we have too much glutamate, we get to a point where we are overdriven:

ASSOCIATED WITH (increasingly bad):

- hyperactive cognition, motor and sensory

- driven, stressed

- anxiety, seizure

.

- your brain speeds up (sometimes in a bad way)

GABA

IF U HAVE TOO MUCH:

- Inhibited cognition, motor and sensory

- relaxed, disinhibited

- malaise, coma

.

- your brain relaxes and things slow down

Normal thinking depends on the balance of:

- excitatory glutamate and inhibitory GABA -> = impaired cognition

- Behaviour and emotions are even more complicated

Serotonin and Dopamine are types of

monoamines

The Monoamine Neurotransmitters

- he uses can't not because they are involved in rewards, euphoria, drive, safety

Dopamine (DA)

ON = activate DA receptors (GPCRs)

- D-1 like (increase cAMP) and D2-like (decrease cAMP) are all GPCRs but act in contradictory ways

.

OFF =

- reuptake - DA transporter (DAT), then...

- broken down by enzymes: monoamine oxidase (MAO), catechol-O-methyl transferase (COMT)

Serotonin

ON = activate 5-HT receptors

- the 5-HT receptors, are GPCRs -> signalling (except 5-HT3 receptor = ligand-gated cation channel) (its ionotropic)

.

OFF = reuptake

- monoamine transporter (SERT), on the presynaptic neuron

- various agents can inhibit 5-HT reuptake, including cocaine, tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) → increase synaptic 5-HT.

How do we use these monoamines

- Neurohormonal control systems

- the limbic system

Neurohormonal Control Systems

- they have common features:

- the original nuclei/driver is located in the brain stem

- a lot of pathways go to prefrontal cortex and basal nuclei and limbic sytem

Reticular Excitatory Area (REA) - ACh system

GENERAL SYSTEM FOR CONTROL OF THE OVERALL LEVEL OF EXCITATION OF THE BRAIN:

- in reticular formation of pons and midbrain

- spreads throughout entire cortex

- causes acutely awake + excited nervous system

RAPID TRANSMISSION (ms) TO EXCITE THE CEREBELLUM:

- gigantocellular neurons: excitatory -> ACh (rapid acting, rapidly destroyed)

MAKES YOUR BRAIN ACUTELY AWAKE:

- ACh from the REA activates lots of other Glutamatergic neurons

SWITCHED FOF BY ITS OWN INHIBITORY AREA (serotonergic)

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WAY TO RMBR: Acutely Awake and Active

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- substantia nigra means black substance

The dopamine system

- substantia nigra, ventral tegemental area - fibres spread to specific regions

- Excitatory or inhibitory (region dependent - different receptors)

Dopamine: main focus/desire neurotransmitter:

- responsible for our drive or desire to acquire (food, sex, an achievement, drug)

- makes people more talkative and excitable, often leaves them wanting more (addiction)

.

WAY TO RMBR: Drive, reward and pleasure

The Noradrenaline System

- from locus coeruleus (pons)

- mostly excitatory; fibres spread through cortex

- involved in numerous activites in the stress response

- the locus coereuleus is activated by stress -> NA -> alters cognitive function (through the prefrontal cortex), increaeses motivation

- pain control (anti-nociceptive)

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WAY TO RMBR: ANxiety, arousal and pain control

The Serotonin System

- From Raphe Nuclei (medulla, pons, midbrain)

- usually inhibitory, fibres to specific cortex regions (dense in frontal lobe and corticolimbic projections)

- Serotonin: main well-being/satisfaction neurotransmitter (it allows us to be content and happy, keeps mood under control by helping with sleep, calming anxiety and relieving depression

- pain control (anti-nociceptive)

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WAY TO RMBR: Safe, happy, relaxed, euphoric and low-pain

The Limbic System EXPLAINED

- a set of structures involved in the processing of emotion, motivation, learning and memory

- core structures: hypothalamus, amygdala and hippocampus (also nuclei of midbrain and brainstem)

- they also work closely with certain circuits through the basal ganglia and cortex

- integrate and involve all the neurohormonal control systems (in different ways)

Hypothalamus - Homeostasis

- plays a role in regulating most basic physiological

- hunger, thirst, temperature, arousal, sleep etc.

- central command centre of the ANS

- receieves signals from the brainstem, (serotonin and dopamine) and integrates to influence behaviours like food intake and mood

Links nervous and endocrine systems - hypothalamus controls the pituitary which controls everything

- hypothalamus produces releasing hormones

- control levels of growth hormone, thyroid hormone, adrenal cortex steroids, sex steroids

Amygdala - Fear, Focus and Reward

- decision making (drive), and emotional responses (including desire, fear, anxiety and aggression)

- emotional arousal and emotional learning (communicates with hippocampus)

- reward (dopamine) pathways too

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- amygdala is triggered if someone has had trauma

Hippocampus = Learning and memory

- regulates memory formation and storage

- regulates glutamate neurotransmission via NMDA receptors

- fed by pleasure (dopamine) and fear (amygdala) pathways

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DONT HAVE TO MEMORISE HTE BOTTOM THING

TAKE HOME MESSAGES

DIAGRAM ON SLIDE 40