Chapter 1

Changes in the ventricular system in schizophrenia

• One of the most consistent findings in schizophrenia is the enlargement of the brain's ventricles

Chapter 2 → Functional Neuroanatomy: The Nervous System and Behavior

Anatomy of the neuron

Lobes of the brain

Forebrain-telencephalon

Basal gangia

Limbic system

Amigdala → regulating anxiety, aggression, fear conditioning, emotional memory, and social cognition.

Hypocampus:

• Located in the forebrain, diencephalon. part of limbic system

• Regulates vital functions including hunger, thirst, temperature, sex

  • sends strong outputs to:

    • midbrain/hindbrain (autonomic function)

    • pituitary (neuroendocrine gland)

Thalamus

• Fear reflex

  • Thalamus to amygdala pathway carries information rapidly to the amygdala

  • The thalamus to cortex to amygdala pathway is slower but allows the external stimuli to be cognitively appraised

Arrangements of cells within the cerebellum

Cerebellum - involved in motor coordination and basic learning

Layers of the cerebellum

• Granule Cell layer (innermost layer)→ composed of small neurons

• Purkinje cell layer (mid-layer) → a single row formed by large cells (purkinje cells)

• Molecular layer (outermost layer) → composed of parallel fibers of granular cells and dendritic trees of Purkinje cells

Systems that Protect and Nourish the Brain

• Ventricular system

  • series of four chambers filled with cerebral spinal fluid (CSF). Lined with choroid plexus, a membrane of cells that produces cerebral spinal fluid.

• Two lateral ventricles in telencephalon

  • one in of each hemisphere, extend s into all four lobes

• 3rd ventricles in diencephalon

  • at the midline between the lateral ventricles

• 4th ventricles in hindbrain

  • CSF can exit here into the subarachnoid space, connect with with the central canal in the spinal cord

Meninges (the 3 protection layers of the brain & spinal cord)

• Dura matter - tought outermost sheet

• Arachnoid - substance between the dura and pia matter that chushons the brain in cerebrospinal fluid (CSF)

  • functions of cerebrospinal fluid (CSF)

    • shock absorber

    • exchange medium btw blood and brain

• Pia Matter - delicate innermost layer

Blood-brain-barrier (BBB)

• Dynamic physical and metabolic barrier between blood and CSF/brain consisting of specialized endothelial cells that protects the brain from blood-borne compounds and maintain homeostasis in the brain

  • Composed by

    • Intercellular pathway → passage of water-soluble molecules

    • Transcellular lipophilic pathway → passive diffusion of lipid-soluble molecules across the barrier

    • Transport protein pathway → active diffusion of large molecules across the barrier by specific proteins

    • Protein pumps → active transport back into the bloodstream of some lipophilic molecules

Corotid arteries

• Major arteries to the brain (three of them)

  • The anterior, middle & posterior cerebral arteries

    • The anterior and middle originate form the internal carotid artery

    • the posterior originates form the basilar artery that itself arises from the vertebral arteries

Ch 3 → Neurophysiology: The Generation, Transmission, and Integration of Neural Signals

Electical signals

• Action potential (AP) → rapid electrical signal that travels along the axon of a neuron

• Neurotransmiter → chemical messenger between neurons.

Ionic basis of the resting potential

• Neuron at rest = balance of electrochemical forces

• Ions → electrically charged molecules.

  • Dissolved in intracellular fluid, separated from the extracellular fluid by the cell membrane

    • Anions → negatively charged

    • Cations → positively charged

  • Sodium-potassium pump

    • maintains resting potential

    • pumps 3 Na⁺ out for every 2 K⁺ pumped in

• Equilibrium potential → K⁺ reaches equilibrium when its movement out is equal to the movement in

  • equilibrium potential of the resting membrane potential is about -65mV (btw -50 & -80mV)

Action Potential

• Brief and large change in membrane potential produced by the movement of Na⁺ ions into the cell

  • originates in the axon hillock and propagates along the axon towards axon terminals

  • carries information to postsynaptic targets

  • unidirectional as a result of the refractory state of the membrane post-depolarization

Membrane Potential

Vocab

• Depolarization → decrease in membrane potential

  • inside of cell becomes more positive

• Repolarization

• Hyperpolarization → increase in membrane potential

  • inside of cell becomes more negative

Membrane potential & refractory period

• Membrane potential at any given time depends on how many and which ion channels are open

• Refractory period → time when only some stimuli can produce an action potential

  • there are two phases of it

    • Absolute refractory period → time where no action potentials can be produced

    • Relative refractory period → time when only strong stimulation can produce an action potential

Steps of Action potential process (through membrane potential graph):

1. K+ creates resting potential (-65 mV)

   1. Open K⁺ leak channels → reached equilibrium potential

   2. Na⁺ are closed

2. Cell become more negative increasing the membrane potential

   1. closed K⁺ channels → K⁺ leak channels allow K⁺ flow in and out → make the cell negative → bring it closer to threshold

3. Absolute refractory period

   1. At threshold (-40mV) voltage gated Na⁺ channels open allowing Na⁺ inside the cell

      1. neurons have an all-or-nothing property that makes it so that a neuron must reach the -40mV threshold for the neuron to fine.

         1. if the threshold is not reach not action potential will occur

   2. the membrane undergoes depolarization until its peak at 40mV

4. Relative refractory period

   1. At 40mV the Na⁺ channels close automatically, K⁺ channels open creating a disbalance that causes afterpotential

   2. membrane undergoes depolarization and then hyperpolarization

5. Membrane returns to its resting potential

   1. all channels close (except K⁺ leak channels)

      1. K⁺ will diffuse in and out the cell while all the anions remain inside the cell allowing it to return to its resting potential.

Conduction in axons

• Conduction velocity → the speed of propagation of AP which varies with the diameter of the axon

  • the smaller the diameter the faster it goes

Unmyelinated axon → axons without myelin sheath

• Since there is no myelin sheath in the unmyelinated axons the conduction of AP in them is slow (10 m/s)

  • invertebrates

Myelinated axon → axons with myelin sheath

• Rapid conduction (150s/m) thanks to myelin sheath

  • vertebrates

• Saltatory conduction along the myelinated axon

  • Saltatory conduction → the axon potential travels inside the axon and jumps from node to node

    • Nodes of Ranvier → small gaps in the insulating myelin sheath

      • axon is exposed

Ion channels

Channelopathy

• genetic abnormality of ion channels often causing a disorder (23 currently identified)

  • Na⁺ channelopathy → various seizure, muscle and cardiac disorders

  • Cl^- channelopathy → associated with deafness, kidnney problems, movement disorders and epilepsy

Channel toxins

• Certain animals contain toxins that block specific ion channels

  • Toxins that block voltage gated Na⁺ channels

    • Tetrodoxin (TTX) → produced in the ovaries of puffer fish

      • Blocks Na+ channels by binding to the outer pore of voltage-gated sodium channels in nerve cells, effectively preventing sodium ions from entering the cell and thus inhibiting the generation of action potentials, leading to rapid weakening and paralysis of muscles, including those of the respiratory tract, which can lead to respiratory arrest and death.

    • Saxitoxin (STX) → produced by algae

      • acts similar to TTX

  • Toxins that force voltage gated Na⁺ channels to remain open

    • Batrachotoxin → produced by poison arrow frogs

      • Binds to and irreversibly opens the sodium channels of nerve cells and prevents them from closing, leading to irreversible depolarization of nerves and muscles, fibrillation, arrhythmias and eventually cardiac failure

Synaptic transmision

• Synapses cause local, graded changes in the postsynaptic membrane potential

  • Synaptic delay → delay between an action potential
    reaching the axon terminal and creating a postsynaptic
    potentia

  • Postsynaptic potential → brief change in resting potential

    • there are 2 types

      • Inhibitory postsynaptic potential (IPSP) → produces a small hyper-polarization, pushing the cell further away from threshold (inhibiting the cell’s ability to produce a new AP)

        • this potential is a result of Cl⁻ ions entering the cell thus making it more negative (below resting potential)

      • Excitatory postsynaptic potential (EPSP) → produces a small local depolarization, pushing the cell closer to threshold

      

Events in Synaptic transmission

1. AP travels down the axon to terminal

2. voltage gated Ca²⁺ (Calcium) open and Ca²⁺ enters

3. Neurotransmitters are released into the synaptic cleft bia exocytosis

   1. Synaptic vesicles fuse with membrane and release the neurotransmitters

4. Neurotransmitters cross the synaptic cleft and bind to receptors in the postsynaptic membrane, causing either EPSP or IPSP

5. EPSP or IPSP spread towards the post synaptic axon hillock

   1. Spacial summation → summing of potentials that come from differents parts of the cell

      1. If the EPSP input is stronger than the IPSP and their sum exceeds the -40mV threshold the axon hillock will produce an action potential

6. Neurotransmitter action is brief it will be either…

   1. Inactivated by enzymatic degradation (6a)…

      1. rapid breakdown and inactivation of transmitter by an enzyme (ex. AchE breaks down ACh and recycles it)

   2. Or removed by transporters for reuptake and recycling (6b)

      1. transmitter is taken up into (endocytosis) the presynaptic cell by specialized transporters (SSRI)

7. neurotransmitters may activate presynaptic autoreceptors resulting decrease of its own release

Receptors in Synaptic transmission

• Receptors are activated/inhibited by ligands

  • two types

    • Endogenous ligands → Produced by the body

      • neurotransmitters (acetylchloride → ACh)

        • ACh is a neurotransmitter that can bind to the nicotinic receptor to allow Na⁺ ions to enter the cell

      • Hormones

    • Exogenous ligands → from outside the body

      • drugs & toxins from outside the body

ACh receptors

• Nicotinic ACh receptors → ligand-gated ion channel

  • located…

    • on muscles

    • in autonomic ganglia

• Muscarinic ACh receptors → G-protein-coupled receptor

  • located…

    • in the brain

    • organs innervated by the parasympathetic division of the autonomic system

  • activated by…

    • ACh & muscarine (found in mushrooms)

Loewi’s demonstration of a chemical messenger

• Otto Loewi's demonstration involved electrically stimulating the vagus nerve of a frog heart, causing it to slow down, then transferring the fluid surrounding that heart to another frog heart, which also slowed down, proving that a chemical substance released by the first heart (acetylcholine) acted as a "chemical messenger" to influence the second heart's rate

  • This experiment provided the first evidence of chemical neurotransmission.

Receptors & receptor controll

• Receptor # in cells are dynamic

  • this is a result of things such as daily changes in adulthood, changes during development and changes of drug use

  • Two types of regulaions

    • Up-regulation → increase receptor #

    • Down-regulation → decrease receptor #

• There are 2 ways in which receptors control ion channels

  • Ionotropic receptors (ligand-gated ion channel)

    • activated by neurotransmitters → direct opening of ion channel → ion enters the cell

      • acts fast → only 2 mol. of neurotransmitters needed for the ion channels to open

    • Example → Nicotinic ACh receptor

      

  • Metabotropic receptors (G-protein-coupled receptors)

    • activated by neurotransmitters → actvation of G-proteins → activation of 2nd chemical (secondary messenger) or activation of nearby ion channel → ion enters the cell

      • acts slow → causes an indirect opening of ion channel

        • 80% of ligands (neurotransmitters and hormones) bind to G-protein-coupled receptors

    • Example → Muscarinic ACh receptors

  

Types of Synapses

• Chemical synapse

  • Chemical substance mediates synaptic transmission form pre to post-synapse

  • Synaptic cleft = 20-40 nm

• Electrical synapse (also known as gap junctions)

  • Ions flow through large channels called connexons into adjacent cells

  • Synaptic cleft = 2-4 nm

  • no synaptic delay!

Chapter 4 → The Chemistry of Behavior: Neurotransmitters and Neuropharmacology

Add on to previous chapter

• 2 types of substances

  • Exogenous substances → substances from outside our own bodies, used throughout human history to affect our physiology and behavior

  • Endogenous substances → substances that naturally occur within the body

• 2 types of receptors

  • Inotropic (fast)→ when activated by a neurotransmitter binding to it the receptor will change in shape

  • Metabotropic (slow)→ when activated by a neurotransmitter binding to it the receptor will alter chemical reactions

Neurotransmitters

• They are Versatile

  • a single neurotransmitter can bind to several receptor subtypes

    • Inotropic (fast)

    • Metabotropic (slow)

  • either type of receptor can exite or inhibit a target cell

Criteria for neurotransmitters

• substance exists in presynaptic axon terminal

• is released when AP reach axon terminals

• receptors of the substance exist in presynaptic membrane

• when experimentally applied, substance induces changes in postsynaptic cells

• blocking the release of the substance prevents changes in postsynaptic cell

Types of neurotransmitters

• Glutamate

  • most prevalent excitatory neurotransmitter

    • plays a role in → cognition, learning and memory

    • binds to both ionotropic (NMDA, AMPA, kainate) and metabotropic (mGLUR1-18) receptors

  • Excitotoxicity → excess glutamate release resulting in damage/loss of neurons

    • plays a role in → Alzheimer’ disease, brain trauma,
      seizure disorders, Parkinson's disease, stroke,
      Huntington's disease, autism, schizophrenia

• GABA (gamma-Aminobutyric acid)

  • most prevalent inhibitory neurotransmitter

    • binds to both ionotropic (GABA_A, GABA_C) and metabotropic (GABA_B) receptors

  • Drugs based on enhancing GABA functions

    • Hypnotics, sedatives, tranquilizers, anticonvulsants

      • most well known → benzodiazepines (Diazepam=Valium)

    • Alchohol, cannabis

    • Used to treat pain, seizures, anxiety and migrane

• Acetylcholine (ACh)

• can be both inhibitory or excitatory

  • binds to ionotropic (nicotinic) and metabotropic (muscarinic) receptors

  • plays a role in → arousal, attention, learning & memory, and motivation

  • damage to cholinergic nerve cell bodies in the brain is associated with Alzheimer’ disease

Monoamine neurotransmitters

• Catecholamines

  • Dopamine (DA)

    • found in neurons in the →

      • Mesostrial pathway originating in the substantia nigra and projecting to the striatum

        • important in motor controll

      • Mesocorticolimbic pathway originating in the ventral tegmental area (VTA) and projecting to the cortex & limbic areas

        • important for reward and aversion, and learning

        • Abnormalities associated with schizophrenia and depression

  • Epinephrine/adrenaline

    • not in the brain

  • Norepinephrine (NE)

    • synthesized in the locus coeruleus (pons) and lateral tegmental system (midbrain)

    • binds to metabotropic (alpha 1, alpha 2; beta1, beta 2, beta 3) receptors

    • modulates mood, arousal, attention, behavioral flexibility and sexual behavior

    • Drugs → beta blocker (proparanolol)

      • reduces preformance anxiety

• Indoleamines

  • Melatonin

    • sleep & wakefulness

  • Seratonin (5-hydroxythryptamine, 5-HT)

    • synthesized in 7 raphe nuclei, with dorsal raphe nucleus being the largest

    • role in sleep, mood, sexual behavior, depression and anxiety

    • Drugs → selective serotonin reuptake inhibitors (SSRI)

      • antidepressants (prozac)

Drugs

Agonistic and Antagonistic Actions of Drugs

a drug can be…

• Agonist → mimics effects of usual neurotransmitter

• Antagonist → binds receptor without activating it, thereby blocking the receptors from being activated

  • competitive vs non-competitive antagonist

    • Competitive antagonist → compounds that compete with agonists for the same receptor, but they do not exert an agonist effect themselves and so reduce the effect of any agonist present

    • Non-competitive antagonist → a compound that prevents an agonist from having a biological response by binding to a receptor protein

• Inverse agonist → binds receptor and initiates opposite effect of usual neurotransmitter

The Effects of a Drug Depend on Its Site of Action and Dose

• Binding affinity → the degree of chemical attraction btw a ligand and a receptor

  • the more affinity a drug has for its receptor the lower the doses

  • neurotransmitters are low-affinity ligands allowing them to dissociate from receptors

• Efficacy (intrinsic activity) → ability of a bound ligand to acctivate the receptor

  • Agonist have high efficacy

  • antagonists have low efficacy

The Dose-Response Curve (DRC)

• ED₅₀ value

  • effective dose for 50% of people recive the drug

  • allows comparison of potency of drugs

    • the higher the potency the more comparable the effects are at lower doses

• Therapeutic index

  • separation between effective dose and toxic/lethal dose

  • determined by comparing ED₅₀ with TD₅₀ (toxic dose for 50% of individuals) or LD₅₀ (lethal dose for 50% of individuals)

Neuroactive Drugs

• Antidepressants

  • Class of drugs used to treat symptoms of depression

    • Monoamine oxidase (MAO) inhibitors

      • prevent breakdown of monoamines at synapses

    • Tricyclic antidepressants

      • prevent the reuptake of serotonin and norepinephrine into presynaptic axon terminals

    • Selective serotonin reuptake inhibitors (SSRIs)

      • same mechanism as tricyclic antidepressants but with fewer side effects

• Anxiolytics (tranquilizers)

  • class of drugs used to trreat anxiety disorders

    • Benzodiazepine agonists

      • act on GABA_A receptors and enhanse the inhibitory effects of GABA

      • safe and and effective for short term use but long-term use is discouraged because of dependency and withdrawal effects.

TopHat questions

Chapter 1

Q1 - Basic components of a neuron

• Dendrite → communication with other neurons

• Synapse → receiving part of a neuron

• Axon → sending part of a neuron

Chapter 2

Q1 - Match the following terms with the correct description

• Axon → Receiver

• Synapse → Sender

• Dendrite → Junction between two neurons

• Myelin sheath → Insulating layer

Q2 - What is the main function of these glial cells? Match with correct response.

• Oligodendrocytes → remove debris from injured cells

• Microglia → form myelin sheath around axons in peripheral nervous system

• Astrocytes → form myelin sheath around axons in central nervous system

• Swann cell → monitor neural activity

Q3 - Which cranial nerves are not motor nerves?

a) Olfactory

b) Trigeminal

c) Vestibulocochlear

d) Optic

e) Hypoglossal

Q4 - Match the spinal nerves with the corresponding spinal cord segments

• lumbar → pelvic

• sacral → base of spinal cord

• coccyx → lower back

• cervical → trunk

• thoracic → neck

Q5 - What are sympathetic functions?

a) constricts the airways

b) stimulates digestion

c) constricts the blood vessels

d) stimulates salivation

e) accelerates heartbeat

f) constricts the pupils

Q6- Match the anatomical navigation terms with the correct laymen term

• anterior → tail end

• lateral → middle

• ventral → sideways

• dorsal → front

• posterior → back

• medial → head end

Q7 - Match brain region with function

• Hypothalamus → hunger

• Amygdala → emotion

• Septum → emotion

• Caudate nucleus → motor control

• Putamen → motor control

• Thalamus → sensory information

Q8 - What are the main systems that protect and nourish the brain?

a) Blood-brain-barrier

b) Choroid plexus

c) Meninges

d) Cerebral hemispheres

e) Ventricular system of the brain

f) Carotid arteries

g) Spinal cord

Chapter 3

Q1 - The sodium-potassium pump is responsible for

a) pumping potassium and sodium into the cell

b) pumping sodium into the cell and potassium out of the cell

c) pumping potassium into the cell and sodium out of the cell

d) initiating an action potential

e) creating a positive net charge inside the cell

Q2 - Match the action to the ion

• K⁺ → maintains resting potential

• NA⁺ → prevents action potential

• Cl^- → required for action potential

Q3- What is the sequence of events from action potential threshold to resting potential?

• 1 → Voltage-gated Na+ channels open

• 2 → Na+ influx (into the cell)

• 3 → Voltage-gated Na+ channels close and voltage-gated K+ channels open

• 4 → K+ efflux (out of the cell)

• 5 → Voltage-gated K+ channels close

Q4 - An action potential is first initiated at the

a) synapse

b) dendrites

c) axon hillock

d) cell body

Q5 - Which process is not involved in chemical synaptic transmission?

a) Electrical conduction across the synaptic cleft

b) Reuptake of neurotransmitters

c) Influx of calcium at the presynaptic membrane

d) Binding to autoreceptors

Q6 - What is the sequence of events starting with a depolarizing stimulus reaching the threshold to mount an action potential (from 1-4)

• 1 → Postsynaptic receptors are activated

• 2 → NA+ enters the cell

• 3 → Neurotransmitters are released in the synapse

• 4 → The action potential is propagated to the axon terminal

Q7 - Place in order from fast to slow

• 1 → Ionotropic synapse

• 2 → Electric synapse

• 3 → Metabotropic synapse

Chapter 4

Q1 - What determines whether activation of an ionotropic receptor can excite or inhibit the target cell?

a) Type of ion that flows across membrane

b) Type of ligand

c) Type of target cell

d) Type of presynaptic terminal

Q2 - What determines whether a metabotropic receptor can excite or inhibit the target cell?

a) Type of target cell

b) Type of postsynaptic terminal

c) Type of ion channel modulated by the metabotropic receptor

d) Type of ligand

Q3 - Indicate all correct characteristics of an ionotropic receptor

a) slow

b) changes shape

c) activates G-proteins

d) neurotransmitter binds directly to the ion receptor

e) alters chemical reactions

Q4 - What determines whether ACh is an inhibitory or excitatory neurotransmitter?

a) type of receptor it binds to

b) whether it is released in the brain or periphery

c) concentration of ACh

Q5 - Match the neurotransmitter with region of synthesis

• serotonin → locus coeruleus

• norepinephrine → substantia nigra

• dopamine → nucleus basalis

• acetylcholine → raphe nuclei

Q6 - What drugs are associated with what neurotransmitter system?

• GABA → Benzodiazepines

• Serotonin → SSRI (antidepressants)

• Norepinephrine → Propranolol

• Opioids → Morphine

Q7 - Drug affinity - Fill in the Blanks

The higher the affinity of the drug, the - lower - the concentration of the drug.

Q8 - An ideal prescribed drug should have ...

a) low ED50

b) low affinity

c) high LD50

d) high TD50

Q9 - What do MAO inhibitors, tricyclic antidepressants, and SSRI's have in common?

a) Stimulate norepinephrine receptors

b) Decrease the synthesis of serotonin

c) Increase serotonin availability

d) Upregulation of postsynaptic serotonin receptors

Practice Exam

Q1 - The sodium-potassium pump is responsible for

a) pumping potassium and sodium into the cell

b) pumping sodium into the cell and potassium out of the cell

c) pumping potassium into the cell and sodium out of the cell

d) initiating an action potential

Q2 - An action potential is first initiated at the

a) synapse

b) dendrites

c) axon hillock

d) cell body

Q3 - Contact points between neurons are called

a) impulses

b) axons

c) synapses

d) nerves

Q4 - The brain and spinal cord are wrapped in protective membranes known collectively as the

a) meninges

b) myelin

c) dura mater

d) pia mater

Q5 - What is not a system that protects and/or nourishes the brain?

a) blood-brain-barrier

b) carotid arteries

c) spinal cord

d) ventricular system

e) meninges