2 cells close together

-Junctions held together by connexons that form channels

-Gap junction (3.5 nm)

-Found in glial and cardiac cells

1) Synthesis and packaging of chemical signal

2) Release of NT

3) Effect on postsynaptic cell (activation or inhibition)

4) Termination of signal

1) Amino acids - glutamate, glycine, GABA

2) Amines - monoamines (ACh, serotonin) and catecholamines (dopamine, norepinephrine, epinephrine/adrenaline)

3) Peptides - enkephalins, endorphins, dynorphins, substance P, neurotensin, neuropeptide Y

1) Synthesized and stored in presynaptic cell

2) Released

3) Action in another postsynaptic cell

4) Termination

Ion gradient used to concentrate the NT inside vesicle (energy works against concenration gradient)

Vesicles acidic inside - one method is letting protons out in exchange for GABA in

Once NTs are packaged into vesicles --> terminal bouton --> attach to active zone

Henry Dale

One neuron will synthesize, store, and release 1 NT

Works for most except some cells that produce peptides AND amines/amino acids

End product inhibition - negative feedback to regulate production of end product

Rate-limiting enzyme - controls how much NT made in cell

Feedback inhibition - enzyme that creates NT is inhibited when enough NT is in cell

Stimulating vagas nerve slows heart rate

2 frog hearts connected by buffer system w/valve; liquid transferred between when valve open

Exp 1: Heart A&B measured w/valve closed -> stimulated vagus nerve -> Heart A rate slows but Heart B rate stays same

Exp 2: Heart A&B measured w/valve open -> stimulated vagus nerve -> Heart A rate slows -> Heart B rate slows a few seconds later

Conclusion: must be substance released upon stimulation of vagus nerve - proved that NT release is chemical

Extra- and intra-cellular pieces, creates pore in membrane -> NT binds to extracellular piece -> channel opens -> ions flow in through channel

ACh and Glutamate - Na+ or Ca+ in - depolarizes

GABA or Gly - Cl- in - hyperpolarize

Now chemical signal converted back to electrical signal

Each NT has various type of channels

Receptor made of single polypeptide chain woven through membrane 7 times

Sometimes called 7-transmembrane receptors

G-protein - complex of protein w/alpha, beta, and gamma subunits; called G because they bind GDP and GTP

ACh muscarinic receptor -> ACh binds to receptor -> G-protein binds -> GTP/GDP exchange, splits apart alpha and beta-gamma subunits -> beta-gamma subunit hits and opens K+ channel -> membrane potential hyperpolarizes

[alpha subunit modifies activity of membrane-bound enzyme, generates chemical compounds that also change membrane potential]

Receptor: GPCR

G-protein: G(s) or G(i)

Effector enzyme: adenylyl cyclase

Substrate of effector enzyme: ATP

Second messenger: cAMP

Protein kinase: PKA

Receptor: GPCR

G-protein: G(q)

Effector enzyme: PIP(2)

Second messengers: DAG, IP(3), CA2+

Intermediaries: IP(3)-R, ER, CaM

Protein kinases: PKC, Ca/CaM

NT activates GPCR and subunits split -> alpha subunit (G(q)) goes to enzyme PLC -> catalyzes PIP(2) which is a lipid in membrane -> splits it to create DAG (stays in membrane) and IP(3) (a sugar) -> PKC is the protein kinase that is activated -> PKC can then phosphorylate channels in cell;

IP(3) binds to a ligand-gated ion channel Ca2+ receptor in ER membrane -> calcium released from ER -> calcium binds to protein CaM to form Ca/CaM complex -> activates another protein kinase called Ca/CaM-dependent protein kinase

EPSP - Excitatory Post-Synaptic Potential, depolarizing potentials, excitatory, positive ions in

IPSP - Inhibitory Post-Synaptic Potential - hyperpolarizing potentials, inhibitory, negative ions in

Spatial - sum of potentials from multiple nearby cells

Temporal - sum of potentials arriving in rapid succession at a single synapse

Measure of how far depolarization will spread across dendrite

Defined as distance where depolarization amounts to 37% of its value at the origin

(length constant = .37 x original depolarization value)

1) Diffusion (used w/some peptide NTs)

2) Degradation (enzymes in synaptic cleft degrade NTs like ACh back into original parts)

3) Reuptake (transporters pump NT back into terminal bouton, remove it from cleft, repackage back into vesicles)

GEFS (generalized epilepsy with febrile seizures) - genetic mutation alters Na+ channel

Tetrodatoxin (TTX, caused by puffer fish) - blocks Na+ channels, no APs -> liver failure, numbness, nausea, paralysis,d eath

Satitoxin (STX, caused by dinoflagellates) - blocks Na+ channels in similar way to TTX

Tetramethylammonium (TEA) - blocks K+ channels

*Remember, depolarization - influx of Na+, repolarization - efflux of K+ !!*

Voltage-gated Na+ channels when V(m) > - 40 mV -> ball-and-chain model of channels: CLOSED/DEINACTIVATED, OPEN, INACTIVATD (during refractory periods)

1 ms delay, then voltage-gated K+ channels open - "delayed rectifiers"

1) Rising phase - rapid depolarization of membrane - ~ -40 mV

2) Overshoot - when inside of neuron is positively charged w/respect to outside

3) Falling phase - rapid repolarization until membrane is more negative than Vm at rest

4) Undershoot - when Vm < Vm at rest

5) Gradual restoration of resting potential

Vm - Eion 

The difference between the membrane potential and the equilibrium potential for a particular ion

gion 

Contribution of ion to total conductance of a membrane?

iion = gion x (Vm - Eion)

Ionic current = ionic conductance x ionic driving force 

Describes net movement of ion across membrane

*Note: if ionic conductance OR ionic driving force is zero, there will be NO net movement of ion!

*Remember: K+ more concentrated inside, Na+ and Ca2+ more concentrated on outside*

Sodium-potassium pump - internal Na+ -> uses ATP -> exchanges internal Na+ for external K+

Calcium pump - actively transports Ca2+ out of cell

1) Amino acids: GABA, Glycine (Gly), Glutamate (Glu), aspartate

2) Monoamines: Acetylcholine (ACh), histamine, serotonin

3) Catecholamines: Dopamine (DA), norepinephrine (NE), epinephrine (E)

4) Peptides: leucine enkephalin, substance P, etc.

IEP = electrical potential difference that exactly balances an ionic concentration gradient (Eion)

4 pts:

1) Large changes in membrane potential are caused by tiny changes in ionic concentration

2) Net difference in electrical charge occurs at the inside + outside surfaces of the membrane

3) Ions are driven across membrane at a rate proportional to the difference b/w the membrane potential and the equilibrium potential (ionic driving force = Vm - Eion)

4) If the concentration difference across the membrane is known for an ion, an equilibrium potential can be calculated for that ion

Voltage across neuronal membrane at any moment

Vm at rest = - 65 mV (inside w/respect to outside)

Movement of electrical charge

Represented I, measured in amps

1) Electrical potential/voltage - force exerted on a charged particle (V, volts)

2) Electrical conductance - relative ability of an electrical charge to migrate from one point to another (g, siemens)

Inverse of electrical conductance - electrical resistance (R, or 1/g)

Electrical current = electrical potential x conductance

I = gv

- main ingredient in intra- and extra-cellular fluid is H20

- Ions - atoms/molecules with net electrical charge (anions and cations)

- Phospholipid membrane - hydrophilic (polar) 'head' w/phosphate and hydrophobic (nonpolar) 'tail' w/hydrocarbons

- Protein: enzymes (catalyze), cytoskeleton (shape), receptors (take up NTs)

Layers of membrane that insulate axoms

- oligodendroglial (CNS) and Schwann cells (PNS)

- nodes of Ranvier - short region where membrane is exposed, speeds propagation of nerve impulses down axon

Number of Neurites: unipolar, bipolar, multipolar

Dendrite Type: stellate and pyramidal, spiny and aspinous

Connection Type: primary sensory neurons, motor neurons, interneurons

Axon length: Golgi Type I (long), Golgi Type II (short axons)

Neurotransmitter type: Cholinergic, peptergic, etc.

Branch from the ends of neurons; form a dendritic tree with dendritic branches

Dendritic membrane under a synapse has many receptors

Dendritic spines cover some neurons, believed to isolate chemical reactions triggered by synaptic activation

Mental retardation: mentally retarded people have fewer dendritic spines, and those they do have are unusually long and thin

Initial segment of an axon

Distinguished from soma by:

1) No rough ER and few-none ribosomes

2) Protein composition of axonal membrane different from soma membrane

End of axon; swollen disk; contacts another cell at the synapse

Cytoplasm is different - no microtubules, many synaptic vesicles, dense protein covering facing synapse, many mitochondria

Point of contact between two cells

Point where NTs are transferred between cells

Synaptic cleft

20 nm

Large, run down neurites, hollow core

Made of tubulin

MAPs - microtubule-associated proteins - anchor MTs to each other and the neuron

5 nm

Smallest cytoskeleton part, numerous in neurites

Made of actin

Role in muscle contraction

Closely associated with the membrane

10 nm

Intermediate filaments in rest of body

Resemble bones and ligaments

Very strong

Stacks of membrane dotted w/ribosomes

Major site of protein synthesis: RNA transcripts bind to ribosomes -> ribosomes translate mRNA to proteins

*If protein is destined for cytosol, it is made by free ribosomes.  If it is destined for membrane of a cell or organelle, it is made in Rough ER*

Chromosomes contain DNA, made of segments of genes

mRNA - 4 nucleic acids, copies DNA through transcription.

Promotor, RNA polymerase, transcription factors, coding sequence, terminator.

Introns, exons, RNA splicing.

Basic dyes, stain nuclei of neurons and clumps of material around nuclei

1) Distinguishes between neurons and glia

2) Allows study of cytoarchitecture

Silver chromate solution, stains small % of neurons in their entirety

1) Revealed exact neuronal structure

2) Distinguishes b/w cell body/soma and neurites (axons & dendrites)

Direction pointing up

(from Latin word for 'back')

Directing pointing down

(from Latin word for 'belly')

Medial - structures closer to midline

Lateral - structures farther from midline

Ipsilateral - two structures on the same side of the midline

Contralateral - two structures on opposite sides

1) Midsagittal plane and sagittal plane

2) Horizontal plane

3) Coronal plane

[image]

Midsagittal plane - the plane of section resulting from splitting the brain into equal right and left halves

Sagittal planes - sections parallel to the midsagittal plane

Rostral-most and largest part of the brain

Split down the middle into two cerebral hemispheres, separated by deep sagittal fissure

Generally R side of cerebrum receives sensations from and controls movements of L side, and vice versa.

Lies behind the cerebrum, name means "little brain" but contains as many neurons as the cerebrum.

Mostly movement control center w/extensive connections w/cerebrum and spinal cord.

L side of cerebellum concerned with movements of L side of body, and same for R.

Forms the stalk from which the cerebral hemispheres and the cerebellum sprout.

Relays info from cerebrum to spinal cord and cerebellum, and vice versa.

Also regulates vital functions - breathing, consciousness, and control of body termperature.

Most primitive part of mammalian brain.

Encased in bony vertebral column, attached to brain stem.

Major conduit of info from skin/joints/muscles to brain, and vice versa.

Communicates via spinal nerves (part of PNS) that exit the spinal cord through notches between each vertebra.

Every spinal nerve attaches to the spinal cord by means of two branches, the dorsal root (on dorsal side of spine in animals like rats) and the ventral root (on ventral side).

Dorsal root - contains axons bringing info INTO spinal cord. 

Ventral root - contains axons bringing info  OUT OF spinal cord.

All spinal nerves that innervate the skin, joints, and muscles under voluntary control.

Cell bodies of motor neurons lie in CNS, but axons are in PNS.

Enter spinal cord via dorsal roots, clusters of dorsal root ganglia outside spinal cord.

Neurons that innervate the internal (and involuntary) organs, blood vessels, and glands.

Visceral sensory axons bring info about visceral function to CNS.  Command contraction and relaxation of muscles in walls of intestines and the blood vessels, rate of cardiac muscle contraction, and secretory function of various glands.

Afferent axons - axons that transport information toward a certain point

Efferent axons - axons that transport information away from a certain point

12 cranial nerves that arise from the brain stem and innervate the head.

Each has a name and number associated with it.

Some in CNS, some in PNS (somatic or visceral).

3 membranes that protect the CNS from coming into direct contact with overlying bone of the skull and vertebral column.

1) Dura mater

2) Arachnoid membrane

3) Pia mater

[image]

[image]

Fluid (CSF)-filled caverns and canals inside the brain.

CSF produced by choroid plexus in ventricles of cerebral hemispheres -> flows from paired ventricles of cerebrum to a series of connected, unpaired cavities at the core of the brain stem -> exits ventricular system and enters subarachnoid space by way of small apertures located where cerebellum attaches to brain stem -> in subarachnoid space CSF is absorbed by blood vessels at arachnoid villi.

Generates an image of a slice of brain by rotating an X-ray source around head within plane of desired cross-section, using sensitive electronic sensors of X-irradiation.  Result: digital reconstruction of position and amount of radiopaque material within plane of slice.

Noninvasively reveal gross organization of gray and white matter, and the position of the ventricles in the brain.

1) Gray matter

2) Cortex

3) Nucleus

4) Substantia

5) Locus

6) Ganglion

1) Endoderm -> lining of many internal organs

2) Mesoderm -> bones of skeleton and muscles

3) Ectoderm -> nervous system and skin

Tube of embryonic ectoderm formed from the fusion of the neural folds.

**The entire CNS develops from the walls of the neural tube!

Tissue that is pinched off the neural ectoderm and comes to lie lateral to the neural tube.

**All neurons with cell bodies in the PNS derive from the neural crest!

1) Forebrain

2) Midbrain

3) Hindbrain

**The entire brain derives from the three primary vesicles of the neural tube!

1) Optic vesicles - grow and invaginate (fold in) to form optic stalks and optic cups, which then become the optics nerves and the two retinas

2) Telencephalic vesicles - form the telencephalon, or 'endbrain', consisting of the 2 cerebral hemispheres

1) Telencephalic vesicles grow posteriorly os that they lie over and lateral to the diencephalon

2) Another pair of vesicles sprout off the ventral surfaces of the cerebral hemispheres, giving rise to the olfactory bulbs and related olfactory structures

3) Cells of the walls of the telencephalon divide and differentiate into various structures

4) White matter systems develop, carrying axons to and from the neurons of the telencephalon

1) Cerebral cortex

2) Basal telencephalon

1) Thalamus

2) Hypothalamus

1) Cortical white matter

2) Corpus callosum

3) Internal capsule

Dorsal surface of mesencephalic vesicle --> tectum

Floor of the midbrain --> tegmentum

CSF-filled space between tectum and tegmentum constricts into a narrow channel called the cerebral aqueduct (connects rostrally with the third ventricle of the diencephalon)

1) Superior colliculus (optic tectum) - receives direct input from eye, controls eye movements via synaptic connections w/motor neurons that innervate eye muscles

2) Inferior colliculus - receives sensory input from ear; impt relay station for auditory information en route to thalamus.

1) Cerebellum

2) Pons

3) Medulla (oblongata)

CSF-filled tube becomes fourth ventricle; continuous with cerebral aqueduct of midbrain.

Medullary pyramids - bundles of axons (white matter) running along ventral surface of each side of the medulla.

Pyramidal tract - synonym for corticospinal tract.

Pyramidal decussation.

Neurons perform many sensory and motor functions; bring auditory info from ear, touch, tongue/taste.

Damage can lead to deafness, anesthesia.

Gray matter of the spinal cord, when seen in cross section, looks like a butterfly.

Dorsal horn - upper part of butterfly's wing

Ventral horn - lower part of butterfly's wing

Dorsal columns - bundles of axons running along the dorsal surface of the spinal cord

Lateral columns - bundles of axons lateral to the spinal gray matter on each side

Ventral columns - bundles on the ventral surface of the spinal cord

Dorsal horn cells receive sensory inputs from dorsal root fibers

Ventral horn cells project axons into the ventral roots that innervate muscles

Intermediate zone cells are interneurons that shape motor outputs in response to sensory inputs and descending commands from brain

1) Cell bodies of cortical neurons are always arranged in layers/sheets that lie parallel to surface of brain

2) Layer of neurons closest to the surface is separated from the pia mater by a zone that lacks neurons; called the molecular layer, or layer I

3) At least one cell layer contains pyramidal cells that emit large dendrites, called apical dendrites, that extend up to layer I where they form multiple branches