BBH 203 Exam 2

Synapses

The junction between neurons

Chemical Synapses

Presynaptic neuron secretes neurotransmitters into synaptic cleft, which bind to postsynaptic neuron

Electrical Synapses

Direct exchanges of ions/molecules at physical junctions between two neurons

Types of chemical synapses (Structural)

1. Axodendritic

2. Axosomatic

3. Axoaxonic

4. Dendrodendritic

Types of chemical synapses (functional)

1. Excitatory

2. Inhibitory

Neural Circuit

A group of neurons and their synaptic connections

Convergence (properties of neural circuits)

Many presynaptic neurons send signals to one or a few post-synaptic neurons

Divergence (properties of neural circuits)

One or few presynaptic neurons send signals to many postsynaptic neurons

Neurotransmitter

The chemical released from the presynaptic neuron that serves as the basis for the chemical synaptic communication

Criteria for a neurotransmitter at a given synapse

1. Substance must be present in presynaptic neuron

2. The substance must be released in response to presynaptic depolarization, and the release must be Ca2+ dependent

3. Specific receptors for the substance must be present on the postsynaptic cell

Amino Acid Neurotransmitters

Glutamate (Glu)

GABA

Glycine (Gly)

Monoamines

Serotonin

Dopamine

Norepinephrine

Synaptic transmission, synthesis, release, and binding

1. Most neurotransmitters 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 down its electrochemical gradient to enter the axon terminal

4. Increased intracellular Ca2+ concentration promotes vesicle exocytosis via interactions between synaptotagmin and SNARE complexes

5. Neurotransmitters diffuse across synaptic cleft and bind to postsynaptic receptors

T/F: Post synaptic potentials are graded

True

Excitatory Postsynaptic Potential (EPSP)

Increase probability of postsynaptic action potentials

EPSPs depolarize the postsynaptic neuron (Vm gets more positive)

Inhibitory Postsynaptic Potential (IPSP)

Decrease probability of postsynaptic action potentials

IPSPs almost always hyperpolarize the postsynaptic neuron (Vm gets more negative)

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

What determines the postsynaptic effect(s) of the neurotransmitter?

The neurotransmitter receptor

Varieties of neurotransmitter receptors

1. Ionotropic receptors

2. Metabotropic receptors

Ionotropic Receptors

-Complexed with ion channels that allow one of more types of ions to pass

- Rapid and transient action, causing a PSP

Metabotropic Receptors

-Most are G protein-coupled receptors

- Two general varieties

(1) Indirect gating of ion channels (2) Activation of 2nd-messenger pathways

-Slow and sustained action, with many potential responses (Including PSPs)

What is the problem with letting synaptic release/binding continue unchecked?

Neurotransmitters must somehow be removed from the synaptic cleft

Two mechanisms for removing neurotransmitters from the synaptic cleft

1. Reuptake- Presynaptic neuron or astrocytes reabsorb NT (Ex: serotonin, dopamine, norepinephrine)

2. Degradation- NTs are broken down

(Ex: acetylcholine)

Glutamate and GABA can be removed by either process

Summary of Synaptic Transmission

1. Most 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 down its electrochemical gradient to enter the axon terminal

4. Increased intracellular Ca2+ concentration promotes vesicle exocytosis via interactions between synaptotagmin and SNARE complexes

5. NTs diffuse across synaptic cleft and 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 reuptake and/or degradation

Acetylcholine (ACh)

Two major receptors:

1. nictotinic (nAChRs, ionotropic) 2. Muscarinic (mAChRs, metabotropic)

CNS: synthesized in basal forebrain and pons

PNS: synthesized at neuromuscular junctions and the autonomic nervous system

Clinical correlates: dementia, myasthenia gravis, dysregulation of autonomic nervous system

Glutamate (Glu)

Most abundant excitatory NT in CNS

-synthesized in brain and spinal cord

Involved in many neural processes and connected to synaptic plasticity

Major receptors:

Ionotropic Receptors: AMPA, NMDA

Metabotropic Receptors: mGluRs

Clinical correlates: Excitotoxicity

GABA (gamma-aminobutyric acid)

The most abundant inhibitory NT

Major receptors:

1. GABAaRs (ionotropic)

2. GABAbRs (metabotropic)

Clinical correlates: Alterations in Huntington's & Parkinson's disease, Alzheimer's disease and other dementia's, and schizophrenia

Serotonin (5-HT)

Functionally prolific: descending pain control, mood, appetite, arousal, and aggression

At least 14 types of receptors (almost all metabotropic)

Synthesized in Raphe Nuclei of brainstem

Clinical correlates: Selective serotonin reuptake inhibitors (SSRIs) prescribed to treat depression, anxiety, and personality disorders

Dopamine (DA)

Functions: motor action selection, reward, general cognition

At least 5 different types of receptors (metabotropic)

Synthesized in midbrain

Clinical correlates: Parkinson's disease, dementia w/ Lewy bodies, schizophrenia, all psychoactive drugs

Norepinephrine (NE)

5 different receptor subtypes (metabotropic)

CNS: Synthesized in locus coeruleus (pons) and areas of the midbrain

- Involved in alertness, arousal, feeding, and reward

PNS: Synthesized in sympathetic division of autonomic nervous system

Drug

Any substance that alters an organism's physiology when ingested (other than nutrients considered necessary to normal functioning)

Pharmacology

The interaction between drugs and living organisms

Neuropharmacology

The interaction between psychoactive drugs and the nervous system

Psychopharmacology

The interaction between psychoactive drugs and cognitive processes

Ligand

A chemical binding to a receptor molecule

T/F: Neurotransmitters are the endogenous ligands of the nervous system

True

Exogenous ligands

Drugs binding to receptors

Psychoactive drug

A drug binding to one or more varieties of NT receptor that causes neurophysiological changes

Agonist

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

Inverse Agonist

An agonist exerting the opposite effect of the NT

Antagonist

A ligand that binds to and blocks other ligands from binding to a receptor

Competitive ligand

A ligand that directly competes with a receptor's NT at the receptor's primary binding site

-Proper agonists and antagonists are competitive

Allosteric modulator

A noncompetitive ligand that binds to a non-primary (modulatory) receptor binding site

-AKA neuromodulator

-Doesn't compete with NT at primary 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

Efficacy

The extent to which a drug activates a receptor after binding

Agonists= high

Antagonists= low or none

Binding Affinity

How strongly a drug binds to its receptors

High affinity drug = effective at lower concentrations

Low affinity drug = effective only at higher concentrations

Do neurotransmitters have a low or high binding affinity?

They are low-affinity ligands

Pharmacokinetics

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

Tolerance

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

Metabolic tolerance

Repeated exposure to a drug enhancing the body's efficiency in clearing it

Functional tolerance

Repeated exposure to a drug leading to reduced efficacy via synaptic plasticity

Receptor downregulation if the drug is agonist

Receptor upregulation if the drug is antagonist

Synaptic plasticity

The nervous system is able to tune synapses

Cross-tolerance

Tolerance of one drug generalizing to other chemically related drugs

Sensitization

Repeated exposure to a drug leading to increased efficacy

Postsynaptic drugs

1. Receptor antagonists

2. Receptor agonists

-Neuromodulators (GABAa receptors)

3. Regulators of postsynaptic receptor density

4. Modulators of intracellular signaling cascades

Presynaptic Drugs (Neurotransmitter Release)

1. Voltage-gated Na+ channel blockers

2. Voltage-gated Ca2+ channel blockers

3. Autoreceptor modulators

-Autoreceptor= receptors on the presynaptic neuron

4. Other modulators of neurotransmitter exocytosis

Drugs in the Synaptic Cleft (Neurotransmitter Clearance)

Reuptake inhibitors and enzymatic inhibitors

Natural selection

Adaptations are selected for and ultimate predominate within a population

Adaptations

Traits increasing the likelihood of reproduction

Ecological niches

Set of environmental opportunities and pressures

Gregor Mendel's (genetics) was linked to Hugo de Vries (evolution)

Genetic mutations are the substrate of evolution on which natural selection acts

The survival of an organism ____________ (increases/decreases) chances that genes are passed to offspring

Increases

Divergent evolution

Accumulation of trait differences between closely relate species, sometimes leading to speciation

Speciation

Formation of new species

Homology

Structural/functional/behavioral resemblance based on common ancestry

Convergent evolution

Independent evolution of similar traits in distantly related species

Homoplasy

Structural/functional/behavioral resemblance based on convergent evolution

Taxonomy

The classification of organisms

Phylogeny

The evolutionary history of a group of organisms

Why can we study other animals in neuroscience?

Evolutionary conservation of neuroanatomy, neurophysiology, and/or behavior

What is generally conserved and what differs across the animal kingdom?

Generally conserved:

1. cellular neurobiology

2. neurophysiology

3. principles of behavior

Differs:

1. Gross neuroanatomy

Common features (homologies) across vertebrate brains

-Approx. bilateral symmetry

-Spinal segmentation

-Hierarchical control

-CNS/PNS

-Functional specialization

Evolution of the Vertebrate Brain Relative Size Differences

Relative sizes, proportions, and locations of brain structures

--> modified based on adaptation to unique ecological niches

Encephalization Quotient (EQ)

The extent of deviation from the linear brain-to-body trend

Hominin

A subgroup of hominids (apes) including modern humans and our ancestors

Where was the largest increase in the brain?

Cerebral cortex (specifically the frontal lobe)

*Side note: the brain size tripled over the last 1.5 mil years*

Downsides of having a bigger brain

1. Long gestation time and difficult birthing

2. Brain growth continues for years after birth, requiring prolonged dependence on parents

3. High metabolic cost

4. Complex genes vulnerable to mutation

Brain regions that fully develop later in life....

1. Tend to have expanded most dramatically over evolution

2. Tend to serve more complex functions

Why did Hominin brain size explode?

-Environmental Models

-Social Models

-Cultural Models

Environmental Models (relative to brain size)

Physical challenges in the environment selected for larger brains

- Dietary factors

- Ecological factors

Social Models (relative to brain size)

Cooperative or competitive interactions selected for larger brains

-Hunting/gathering prowess

-Sexual selection

Sexual selection

A form of natural selection in which members of one sex favor specific heritable traits in the other sex during mating behavior

Cultural Models (relative to brain size)

Hominins able to retain and teach accumulated knowledge were more likely to reproduce

Evolutionary Psychology

A research field that studies how natural selection has shaped the behavior of humans and other animals

3 layers of the human embryo during gastrulation (approx. 14-21 days after conception)

1. Ectoderm

2. Mesoderm

3. Endoderm

*Side note- nervous system is one of the first organ systems to develop (day 18-19)*

The ________ induces formation of the neural plate from ectoderm

Notochord

(Day 18-19)

Neurulation- Formation of the Neural Tube

-Neural plate gives rise to neural tube (CNS) and neural crest (PNS+) (days 21-28)

-Rostral and caudal neuropores close, giving rise to the early brain and spinal cord (days 24-25 and 25-26)

Subdivisions of the Neural Tube-Primary Vesicles (3)

1. Prosencephalon (forebrain)

2. Mesencephalon (midbrain)

3. Rhombencephalon (hindbrain)

"Probe Me Right"

Subdivisions of the Neural Tube-Secondary Vesicles (5)

1. Telencephalon: Cerebrum (cerebral hemispheres)

2. Diencephalon: Thalamus + Hypothalamus

3. Mesencephalon: Midbrain

4. Metencephalon: Pons + Cerebellum

5. Myelencephalon: Medulla

"Tell Di: Mes Met My!"

Which secondary vesicles derive from which primary vesicles

1. Forebrain---> Telencephalon, Diencephalon

2. Midbrain---> Mesencephalon

3. Hindbrain---> Metencephalon, Myelencephalon

Neural tube defects are often associated with

Maternal folic acid insufficiency

Anencephaly

-Failure of rostral neuropore closure

-Partial of complete absence of brain, cranial defects

-Most fetuses do not survive to term

Spina Bifida

-Failure of caudal neuropore closure

-Can be largely asymptomatic of involve a herniated sac

-Can often be surgically corrected

*Think Derek Shepards kid*

Fetal Alcohol Syndrome (FAS)

-Can result from maternal alcohol consumption

-Altered facial features, stunted growth

- Often intellectual disabilities, absent corpus callosum in severe instances

Autism Spectrum Disorder (AUS)

-Speculated to have both genetic and environmental causes

-Marked by impaired social interactions, language utilization, a narrow range of interests, and perseveration

Phenylketonuria (PKU)

-Recessive genetic disorder involving inability to metabolize the amino acid phenylalanine

- Susceptible to intellectual disability, especially before age 2, if phenylalanine is consumed in diet

Down Syndrome

-Trisomy 21

-Marked by intellectual impairment, stunted growth, various physical abnormalities

-Increased risk of epilepsy (seizure disorders) and Alzheimer's disease

Stages of Cellular Neurodevelopment

1. Neurogenesis

2. Cell migration

3. Differentiation

4. Synaptogenesis

5. Apoptosis

6. Synaptic remodeling

Neurogenesis

Stage 1 of cellular neurodevelopment

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

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