BBH 203 Part 2

Synapses

The junctions between neurons where signaling between them occurs

Chemical Synapses

Discontinuous, far more numerous (~100 trillion human brain)

Electrical Synapses

Continuous, direct exchanges of ions & molecules between two neurons

Types of chemical Synapse

Presynaptic neuron, and Post Synaptic Neuron

Presynaptic neuron

the neuron at the synapse sending a signal

postsynaptic neuron

the neuron at the synapse receiving a signal

Structural types in the chemical synapse

axodentritic, axiomatic, axoaxonix, dendrodendritic

Functional types -chemical synapse

Excitatory, and inhibitory

Functional types for CS- Excitatory

Synapses that make action potentials in the postsynaptic neuron more likely

Functional types for for CS- Inhibitory

Synapses that make action potentials un the Postsynaptic neuron less likely

from what neurotransmitter chemical released serves as the basis for chemical synaptic communication

presynaptic

Small molecules Neurotransmitters - Amino Acids

Glutamate (Glu), GABA, Glycine (Gly)

Small molecules Neurotransmitters - monoamines

Serotonin (5-HT), Dopamine (DA), Norepinephrine (NE), Epinephrine (Epi), Histamine (HIS)

Synaptic Transmission- Synthesis, Release, and Binding

1. Most neurotransmitters are synthesized in presynaptic axon terminal and stored in synaptic vesicles

2. An AP reaches the axon terminal to activate voltage-rated Ca^²+ channels

3. Ca²+ moves according to its electrochemical gradient to enter the axon terminal.

4. Increased [Ca²+] intra promotes vesicle exocytosis (synaptic vesicles release neurotransmitic toxins) via interactions between synaptic fusion proteins

5. NT’s diffuse across synaptic cleft and bind to postsynaptic receptors

What happens next? and how does this represent signaling between neurons?

Postsynaptic Potentials (PSPs)

Two general electrochemical possibilities that can occur when a NT binds to a postsynaptic receptor.

PSPs are..

Graded Potentials (not action potentials)

Excitatory postsynaptic potentials (EPSPs)

Increase probability of action potentials in postsynaptic neurons

-EPSPs depolarize the postsynaptic neuron (Vm gets more positive)

Inhibitory postsynaptic potentials (IPSPs)

Decrease probability of action potentials in postsynaptic neuron (Vm gets more negative)

As graded potentials, PSPs can sum with one another? True or false

True

Spatial Summation

PSPs arriving in rapid succession from different presynaptic sources sum

Temporal Summation

PSPs arriving in rapid succession from the same presynaptic source sum

Summation makes it more or less likely to reach action potential threshold in the postsynaptic neuron?

True

Can action potentials sum with each other?

No

Neurotransmitters receptors

Membrane protein that bind specific NTs and certain drugs with high specificity

Neurotransmitters receptors - Receptors (and not the NT itself) determine the postsynaptic effect(s) of the NT

True

There is no multiple varieties of receptors associated with most NT’s

False

Neurotransmitter Receptors: Two general receptors

-Ionotropic receptors, -Metabotropic receptors

Ionotropic Receptors

-Complexed with ion channels that allow one or more types of ions to pass into and/ or out of the postsynaptic neuron

-Activated rapidly & transiently - activation causes a PSP

Metabotropic Receptors

Most are G protein-coupled receptors (GPCRs). Two general varieties

1. Receptors that indirectly gate of ion channels when activated

2. Receptors that activate 2nd messenger pathways when activated

-activated in a slow & sustained manner

“Shutting off” the synapse - Problem with letting synaptic release/binding continue ad infinitum?

This can cause desensitization of receptors, disrupt normal neural signaling, and impair synaptic plasticity.

Solution to “shutting off” the synapse

neurotransmitters must somehow be removed from the synaptic cleft.

Removal mechanisms:

diffusion: Nts randomly move out of synaptic clef

reuptake:presynaptic neuron or astrocytes resorb NTs. Ex: serotonin, norepinephrine, GABA, glutumate

Enzymatic degradation: Nt’s are broken down. Ex: Acetycoline, GABA, glutamate

Synaptic Transmission full summary

1. Most neurotransmitters (NTs) are synthesized in presynaptic axon terminal and are stored in synaptic vesicles

2. An AP reaches the axon terminal to activate voltage-gated ca²+ channels

3. Ca²+ moves according to its electrochemical gradient to enter the axon terminal

4. increased [Ca²+]intra promotes vesicle exocytosis via interactions between synaptic fusion proteins

5. NTs diffuse across synaptic cleft bind to postsynaptic receptors

6. Nt-receptor binding triggers some effect in the postsynaptic neuron

7. NTs unbind and are removed from the synaptic cleft through diffusion, reuptake, and or degradation

Drugs

any substance, other than nutrients considered necessary to normal functioning, that alters an organisms physiology when ingested

-not be necessary for survival

Pharmacology

the interaction between drugs and living organisms -or the biomedical field that studies these interactions

Neuropharmacology

The interaction between drugs and the nervous system

Psychopharmacology

the interaction between drug and cognitive processes

Endogenous

internal cause

Exogenous

external cause

Ligand

A chemical binding to a receptor molecule

neurotransmitters are the…

endogenous ligands of the nervous system

Drug bindings to receptors….

exogenous ligands

Agonist

a ligand that binds to and activates a receptor, mimicking the action of the NT

Antagonist

a ligand that binds to and blocks other ligands (including NT’s) receptors

Competitive ligand

a ligand that directly competes with a receptors NT and the receptors primary binding site

Proper agonists and antagonists are competitive yes or no

yes

Allosteric modulator

a noncompetitive ligand that binds to a non primary (modulator) receptor binding site

-doesnt compete with NT at primary receptor binding site

-can be positive (agonist-like) or negative (antagonist like)

Pharmacodynamics

the factors that affect the relationship between a drug and its target receptors

Efficiency

the extent to which a drug activates a receptor after binding

Efficiency-Agonist

Agonist have high efficiency

Efficiency - Antagonist

antagonist have low or no efficacy

Binding affinity

how strongly a drug binds to its receptors

High affinity ligand

binds comparatively well to receptors at lower concentrations

Low affinity ligand

binds well to receptors only at higher concentrations

Pharamacokinetics

the factors that affect the movement of a drug into, through, and out of the body

The blood brain barrier (BBB) affects pharmacokinetics in the CNS

-Psychoactive drugs can permeate the BBB

-Many other therapeutic drugs can’t

Drug tolerance -tolerance:

repeated exposure to the same dose of a drug resulting in a lesser effect

How to overcome tolerance

take a break, increase dose

drug tolerance: metabolic tolerance

repeated exposure to a drug enhancing the body’s efficiency in clearing it (through liver or kidneys)

functional tolerance

repeated to a drug leading to reduced drug efficacy

functional tolerance- receptor downregulation

slows things down (reduces receptors) if drug is agonist

functional tolerance- receptor upregulation

more sensitive to a drug- increase # in receptors if drug is antagonist

cross-tolerance

tolerance built up against one drug generalizing to other chemically related drugs

Chemical synapses

-can amplify signal (one neuron can synapse on many neurons)

-can effect neural computation

-are highly plastic (modifiable)

-far more numerous than electrical synapses (>100 trillion in the human brain)s

Electrical synapses

-Pacilitate more rapid

precise communication

-useful for large scale synchronization of neurons

-Invovle less energy expenditure and infrastructure

Neural circuitry

a group of neurons and their synaptic connections

Neural circuitry-possible properties

-Linearity (neural chain)

-convergence: many presynaptic neurons send signals to one or a few postsynaptic neurons

-divergence: one or a few presynaptic neurons send signals to many postsynaptic neurons

Ectoderm

nervous system

Nervous system one of the first organ systems to develop true or false

true

Notochord

induces formation of neural plate from ectoderm

Neural plate gives rise to neural tube ____ and neural crest______

brain and spinal chord (cns, psn

rostral and caudal neuropores (neural tube) close at days 24-25 and days 25-26, respectively giving rise to early brain and spinal cord true or false

true

Three separate swellings or vesicles from around day 24-25 in the ,,,

rostral. portion neural tube

prosencephalon

forebrain

mesencephalon

midbrain

rhombencephalon

hindbrain

caudal neural tube corresponds to the developing______

early spinal chord

Five separate secondary vesicles develop from the primary vesicles in the rostral neural tube during week 5 true or false

true

Telencephalon- neural tube

cerebrum (cerebral hemispheres)

Diencephalon-neural tube

thalamus & hypothalamus

Mesencephalon-neural tube

midbrain

metencephalon-neural tube

pons & cerebellum

myelencephalon-neural tube

medulla

caudal neural tube continues to develop into the spinal cord at this stage true or false

true

neural tube- filled with…

cerebrospinal fluid

Neural tube defects patron associated with….

folic acid insufficiency

Anencephaly-definition

is a severe birth defect where the upper part of the neural tube fails to close during fetal development, resulting in the absence of significant portions of the brain, skull, and scalp. 

Anencephaly

-failure of telencephalon neuropore closure, partial or complete absence of brain, cranial defects

-most fetuses do not survive to term

Spina bifida

-failure of caudal neuropore closure

-can be largely asymptomatic or involve a herniated sac

other neurodevelopment disorders

includes fetal alcohol syndrome (FAS)

-can result from maternal alcohol consumption during pregnancy

FASDs neurological s/sx

-intellectual/cognitive disability (memory, attention, impulse control etc)

-sensory deficits (vision hearing)

-absent facial features in severe instances

Autism spectrum disorder causes

-speculated genetic and environmental etiologies (causes)

-some comorbidity (autism spectrum disorder) with attention deficit hyperactivity disorder (ADHD)

-Anatomically: hyper connectivity in frontal/temporal lobes

-Behaviorally (can include): impaired social interactions, “stimming” , delayed language acquisition, narrow range of interests, perserveration- persistence in behavior absent stimulus

Stages of cellular neurodevelopment

1. neurogenesis

2. 2. cell migration

3. differentiation

4. synatogenesis

5. 5. apoptosis

6. synaptic remodeling

   -these processes occur over the life span

Neurogenesis

-neural stem cells divide via mitosis to form neurons and glia

-majority of neurons formed by birth, but limited adult neurogenesis

Cell migration

-New neurons and glia are guided by cell adhesion molecules (CAMs) to migrate within neural tube

Differentiation

-after migrating, neurons and glia express different genes to differentiatiate

-assume specific structural & functional identities

induction- differentiation influenced by neighboring cells

Synaptogensis

Axonal and dendritic growth cones project flipodia

Flipodia

pull the growth cone (and axon/dendrite) along to form synapses with target neurons or cells

-growth cones guided by chemoattractants (e.g., CAMs) released by target neurons or cells

-can be repelled by chemorepellents

Chemorepellents

conveying chemical signals to immune cells that instruct them to leave or stay away from a targeted area or tissue in order to restore the tissue to a normal state.

Apoptosis

programmed cell (neuronal) death

-many factors influenced apoptosis

—insufficient neurotrophic factor release from synaptic partner neurons or target cells can trigger apoptosis

Apoptosis - Why produce neurons, only to kill them?

which neurons are serving vital roles determines who one is kept.