Neurobiology Midterm

the study of the structure of the body and the relation of its parts to each other

• The
• study of the structure of the nervous
• system
• •The
• nervous system and the endocrine
• system control
• the body
• –They maintain homeostasis
• »The
• body’s internal environment stays with in physiological parameters of
• temperature, salinity, etc.
• –The mediate movement and behavior
• –The nervous system is only ~3% of your total body weight…
• •…but the brain alone contains over a trillion
• cells
• –~100 billion of these are neurons
• »The
• rest are glia

• –The
• central nervous system
• •Brain, spinal cord
• –The peripheral nervous system
• •Afferent neurons
• –Sensory input
• •Efferent neurons
• –Motor output
• •Connected to the nervous system are:
• –sensory receptors
• –effector tissues
• •muscles
• •glands

• •The somatic nervous system:
• –Mediates
• interaction with external
• environment
• •Afferent nerves come from sensory receptors
• –Eyes
• –Skin
• –Ears,
• etc.
• •Efferent nerves go to muscle effectors

• •The autonomic nervous system:
• –Mediates interaction with internal
• environment
• •Afferent nerves come from internal organs
• •Efferent nerves go to endocrine effectors

• top of head/back - dorsal
• front of chest/bottom of brain - Ventral
• front of head/top of chest - anterior
• bottom of chest/top of head - posterior

•The forebrain is the major structure seen if you look at a brain

• –The
• forebrain is dominated by the cerebral
• cortex
• •This region is also called the telencephalon

• –The cerebral cortex mediates:
• •Voluntary
• movement
• •Cognitive
• processes:
• –Learning,
• speech, math
• –The forebrain includes the thalamus
• and the hypothalamus

•This region is also called the diencephalon

• –The longitudinal fissure
• separates the cerebral cortex into the left and right cerebral hemispheres

• •Each hemisphere is separated into 4 lobes:
• –Frontal, parietal, occipital, temporal

–Lobes defined by fissures

• •The smaller fissures are usually called sulci
• (SUL-ki or SUL-see)

• –Central sulcus, lateral sulcus
• (SUL-kus)

• •The ridges are called gyri
• (JI-ri)
• –Precentral gyrus, postcentral gyrus

• –Thalamus
• •Relays
• sensory inputs
• –Hypothalamus
• •The
• “master gland”
• –Controls
• the pituitary

• »Growth, sperm and egg formation, lactation
• –Controls
• motivated behaviors
• »Eating,
• drinking, sex
• –Controls
• circadian rhythms

• –Important
• for the motivated behaviors of “the 4-Fs”:

• •Fleeing
• •Fighting
• •Feeding
• •Sex
• –The
• amygdala
• plays an important role in the emotion of fear.
• –The
• hippocampus plays
• an important role in learning.

• •The “brain stem” evolved long ago
• –Midbrain
• (mesencephalon)
• •Substantia nigra, pineal gland
• –Hindbrain
• •Medulla, pons and cerebellum

• •Functions of the hindbrain and midbrain:
• –Coordination of movement
• –Homeostasis:
• breathing, blood pressure, digestion, heart rate
• –Filters information between forebrain and rest of nervous system

• •Speech: frontal lobe
• •Emotion: limbic system
• •Movement: cerebellum
• •Memory:
• –Long term: hippocampus (limbic system) and frontal lobes
• –Short term: parietal, temporal, and occipital lobes
• •Vision: thalamus and occipital lobe
• •Taste: thalamus and frontal lobe
• •Touch: thalamus and parietal lobe
• •Hearing: thalamus and temporal lobe
• •Smell: frontal lobe

• •Enlargement of the cerebral
• cortex is the most dramatic distinction
• between humans and “lower” animals

• –Brain evolution is accompanied by increasing
• •Centralization
• •Hierarchical organization
• •Encephalization
• Plasticity

• •Inherited variation
• acted on by

• •Natural selection
• leads to

•Descent with modification

• •As environments change, different individuals
• will be better suited to the new situation
• •If more individuals are created than can
• survive, there will be a struggle for existence

• –The best suited will leave the most offspring
• •This is called fitness

• –The least suited will leave fewer, or no, offspring
• •The next generation will therefore contain
• more of the genes that contribute the best fitness
• –In each generation, the population undergoes adaptation to the environment
• Adaptation over time is evolution

–Over time, structures change, but exhibit homology

• •The lipid bilayer
• serves as a barrier:
• –Allows
• energy to be concentrated inside the cell
• –Allows gradients
• to be built across the membrane
• •A gradient of ions is critical to nerve cell function

• –Channel proteins
• and signal proteins
• mediate:
• •Building ion gradients
• •Responding to neurotransmitter signals

• •The nucleus contains the DNA
• –Genes are made of DNA
• –Genes make proteins which give cells their properties

• •The elaborate shape of nerve cells is
• maintained by the cytoskeleton

• •Neurons are specialized for:
• –receiving,
• –conducting,
• –transmitting
• electrical and chemical signals

• •The ends of the axons make synapses with other neurons
• –The terminal button
• contains vesicles
• of neurotransmitters

• Neurotransmitters:
• chemicals that signal between neurons

• •Oligodendrocytes and Schwaan cells
• protect and insulate axons with a myelin sheath

• •Others:
• –Astrocytes

–Microglia

• •Cell-cell communication involves signals and receptors
• •The signal has to interact with a receptor to
• start the signaling process
• –The signal is a ligand

• •It binds the receptor
• •Cell-cell communication involves signals and receptors
• •The signal has to interact with a receptor to
• start the signaling process
• –The signal is a ligand

•It binds the receptor

• -Direct contact allows materials to pass directly from one cell to another
• Ions, small molecules, action potentials
• - Diffusible molecules can travel in the blood, or across a synapse
• Neurotransmitters
• ..Acetylcholine, epinephrine
• Hormones
• ..Estrogen and testosterone
• Insulin

Or through direct contact

Neurotransmitters: chemicals that signal between neurons

The channels open when the neurotransmitter binds to them

When they open, Na+ and K+ pass through the channels in the membrane

The result is an action potential

G-protein coupled receptors, or GPCRs, get their name because they act through G-proteins

• –GPCRs
• have many effects on cells
• We will be calling GPCRs “metabotropic” receptors, because they act by influencing cellular metabolism.

In the visual system, light activated G-protein coupled receptors and initiates an action potential

Any thing will flow naturally from high to low

The stored energy is released in the process


The amount of energy does not have to be very much to convey information!

All cells spend chemical energy - ATP - to build gradients of ions across their membranes:

The sodium-potassium pump (or: Na-K ATPase pumps Na+ out and K+ in


The result is Na+ high out, K+ high in

• •But, the K+ is
• able to leak out, and proteins trapped inside the cell are negatively charged
• (“A-”)
• •The result is more + out than in, and more - in than out
• –This
• gives the cell an electrical charge
• •The charge is a resting potential of -70 millivolts

• –Minus
• because the inside is more negative than the outside

• •If Na+ channel
• proteins open up, the gradient will dissipate
• –Ions
• will flow naturally down their concentration gradients if allowed to
• •If Na+
• channels open fully, the electrical charge will go from -70 mV
• to 0 mV
• –This
• change in electrical charge is the action
• potential
• •Occurs
• in excitable cells:
• nerves, muscles

• The Na+ channels will open fully only after the cell becomes slightly less polarized
• The required amount of depolarization is called the threshold
• Once initiated, an action potential is all-or-none

• The initial depolarization that triggers an action potential can be the result of neurotransmitter signaling from another neuron
• (Other depolarizing events also exist)
• The neurotransmitter binds its receptor

• The receptor is a chemically gated ion channel
• The receptor is ionotropic
• Na+ rushes in and the membrane depolarizes
• Neurotransmitters are rapidly degraded, ending the signal

• •Not all neurotransmitter signaling results in
• an action potential in the postsynaptic neuron

• –Some
• synapses are excitatory:

• •EPSP: excitatory post synaptic
• potential
• –Open
• Na+
• channels
• –Some
• are inhibitory:
• •IPSP: inhibitory post synaptic
• potential
• –Open
• K+
• channels or Cl-
• channels
• –EPSPs
• and IPSPs are graded
• potentials:
• •Their
• magnitude varies: some are large, some are small
• •In addition, single signals may be too small
• to overcome the threshold
• –<1 mV each
• •Summation can occur:
• –temporal and spatial summation occur
• –Summation
• between EPSPs and IPSPs
• can result in no change in membrane potential
• What counts is the net effect of EPSPs and IPSPs

There are two types of channels:

Chemically gated


Electrically gated


--If the chemically gated channels open enough to pass the threshold, electrically gated channels open

• 1. At rest, the neuron has all its channels closed
• Membrane potential is -70 mV
• 2. If neurotransmitters open up enough chemically gated Na+ channels, electrically gated channels open and Na+ rushes in
• 3. The membrane becomes depolarized
• 4. Once the action potential has occurred, Na+ channels close and K+ channels open

• -Once the K+ channels open, the + charges leave the cell and membrane potential returns to 0
• 5. Too much K+ leaves, but the cell soon returns to normal

The whole process takes 3-4 milliseconds


Until the cell returns to normal, it cannot fire another action potential:


This is called the refractory period

• The refractory period ensures that an action potential will only travel “forward”
• The electrical charge change travels within the neuron just like electricity in a wire.
• When it hits the next section of the neuron, it triggers a new region of action potential
• The action potential cannot move “backward” because that section of neuron is in its refractory period
• Once the action potential reaches the synapse…
• Ca2+ channels open
• Ca2+ enters
• This triggers release -- exocytosis -- of the neurotransmitter
• etc etc etc

• Many neurons have a myelin sheath
• The myelin sheath is interrupted at nodes of Ranvier
• Myelinated neurons are specialized to conduct action potentials very far, very fast:

• The action potential does not dissipate once formed due to the insulation of the myelin
• The current travels to the next exposed region of plasma membrane: the next node of Ranvier
• There, ion channels open and a new action potential begins
• This jumping is called saltatory conduction

• Neurotransmitters are synthesized in the cell body and transported down the microtubules to terminal button:
• Packaged into vesicles and transported by motor proteins

• •Neurotransmitters are released when an action
• potential reaches the terminal button of the presynaptic neuron
• –Ca2+ enters the presynaptic
• cell
• –Ca2+ causes synaptic vesicles fuse
• with the plasma membrane
• –Neurotransmitter
• is released into the synaptic
• cleft
• •The neurotransmitter diffuses across the
• synapse and interacts with receptors in the postsynaptic neuron
• •The receptor
• for the neurotransmitter is a chemically gated ion channel
• –Binding
• of neurotransmitter to receptor ion channel opens the ion channel
• –Na+ rushes in and the membrane depolarizes
• •If
• depolarization is sufficient, a new action potential is initiated
• –In
• more detail, recall: summation of EPSPs
• and IPSPs

• •Neurotransmitters do not stay in the synapse
• for long

• –The
• are taken up: reuptake

• •Special
• transporter proteins bring the neurotransmitter back into the cell that
• released

• –It
• is recycled to make more neurotransmitter

• •They
• can also be taken up by the postsynaptic neuron, or by glial
• cells

• •Cocaine
• binds to the reuptake protein and prevents dopamine reuptake

• –They
• are rapidly degraded

• •Acetylcholine
• is broken down by acetylcholinesterase

• •The
• nerve gas, sarin, is an acetylcholinesterase
• inhibitor

• –Causes
• “SLUDGE”: salivation, lacrimation, urination,
• defecation, gastrointestinal upset, emesis

• •Ionotropic
• receptors:

• –These
• are chemically- (ligand) -gated ion channels.

• –Binding
• of neurotransmitter:

• •Opens
• Na+
• channels

–Depolarization

»EPSP

• •Opens
• K+
• channels

–Hyperpolarization


»IPSP

• •Opens
• Cl-
• channels

–Hyperpolarization


»IPSP

• –Whole
• different thing!
• –G
• protein-coupled receptors
• •“GPCR”
• –Initiate
• signal transduction
• •G
• protein activates enzymes inside the cell
• •Enzymes
• synthesize a second messenger
• •Second
• messengers have diverse effects
• –May
• open channels and initiate EPSP or IPSP
• –May
• influence gene expression
• Metabotropic
• receptors initiate long-lasting changes in the cell

•2 types:

• –Small
• molecules

•Acetylcholine

• •Amino
• acids

–Glutamate

•Monoamines

–Dopamine

»catecholamine

–Serotonin

»Indolamine

• •Soluble
• gases

• –Nitric
• oxide

• –Peptides
• (small proteins)

•Endorphins

–Met-enkephalin:


»tyr-gly-gly-phe-met

• Major neurotransmitter at neuromuscular junctions
• The Botulinum toxin type A (Botox) acts by inhibiting release of Ach at neuromuscular junctions
• Used as treatment for muscle spasm (dystonia)
• (and wrinkles)

•Two major ones:

–Glutamate

• •Most
• common excitatory (EPSP) neurotransmitter in the CNS

• –Acts
• on the ionotropic NMDA and AMPA
• receptors:

• »Important
• in learning

• –Also
• acts on metabotropic receptors

• »Glutamate
• agonists
• being tested for schizophrenia, Parkinson's

• –Gamma-amino
• butyric acid (g-amino butyric acid (GABA))

• •Most
• common inhibitory (IPSP) neurotransmitter in the CNS

• –Acts
• on an ionotropic Cl- channel

• »Agonists
• include benzodiazepines (Valium, Xanax,
• etc.), barbiturates, muscimol from Amanita muscaria

• –Inherited
• mutations in the gene that breaks down GABA leads to loss of inhibition =
• epilepsy

•Two types:

–Catecholamines

• •Most
• important is dopamine

–Excitatory

• »Low
• levels associated with Parkinson’s (treated with L-DOPA), ADHD

• »Increased
• levels associated with addictive behavior (amphetamines and cocaine increase
• dopamine levels), paranoia, schizophrenia

• –Acts
• on metabotropic receptors

• »Phenothiazine
• antipsychotics (chlorpromazine) antagonize dopamine binding to D2 receptors

–Indolamines

• •Most
• important is serotonin

–Inhibitory

• »Decreases
• in serotonin levels can cause depression

• »Drugs:
• Selective serotonin reuptake inhibitors (SSRIs)
• such as Prozac, Zoloft, Paxil used to treat depression

• »LSD
• is an antagonist -- inhibits serotonin signaling -- resulting activation may be
• the underlying cause of the effects f LSD

•Most important one is nitric oxide

• –In
• the brain, may influence K+ channels

• •Inhibiting
• K+
• channels slows recovery from action potential, inhibits signaling

• –Can
• influence release of neurotransmitter

• –Dilates
• the blood vessels by relaxing smooth muscle lining the arteries

• •“nitrates”
• for chest pain

• –Nitroglycerine
• for heart attacks

•Viagra

• –Dilates
• blood vessels in the penis

• Leads
• to erection

• Over 100 neuropeptides known
• ...Peptides are short proteins, made of amino acids
• Most important may be the endorphins
• ....Peptides that activate analgesic systems
• ....Receptors bound by opiates
• -Hence name: endogenous morphine = endorphin
• -Released in a portion of the limbic system
• -.....Release stimulated by alcohol, cocaine

• –Another
• peptide (not an endorphin): made in the hypothalamus, controls eating

• –Stimulates
• feeding:

• •Infusion
• induces frantic feeding behavior

• –Release
• stimulated by

• •Low
• glucose levels

• •Empty
• signals from the stomach

• –Release
• inhibited by

• •Leptin:
• a signal from fat cells

• –Another
• neuropeptide
• –Modulates
• pain reception
• •Sequence:
• Arg Pro Lys Pro Gln
• Gln Phe Phe
• Gly Leu Met