Psych 330H Exam 2

what makes a neurotransmitter?

• exists in presynaptic axon terminals

• synthesized in presynaptic cells

• released during action potential (crosses synaptic cleft)

• receptors on postsynpatic membrane

• produces a postsynpatic membrane potential

what are the 2 types of chemical synpases?

• ionotropic

• metabotropic

ionotropic

• neurotransmitter binds directly to channel protein and ions flow across membrane

• direct and faster

• nicotinic acetylcholine receptor

metabotropic

• neurotransmitter binds G-protein coupled receptor

• more chances to modify

• amplification

• slow but widespread effects

• muscarinic acetylcholine receptor

major classes of neurotransmitters

• acetylcholine

• amino acids

• neuropeptides

• monoamines

• nitric oxide

acetylcholine/cholinergic receptors

• nicotinic

• muscarinic

nicotinic

• named after agonist nicotine (binds receptors)

• excitatory

• ionotropic receptors

  • ACh binding opens a cation channel

  • net ion movement depolarized the postsynaptic cell

• found in skeletal muscle

  • neuromuscular junction

• antagonized by curare (dart poison)

muscarinic

• metabotropic G protein-coupled receptors

• slower, longer-lasting effects

• M1-M5

  • M1, 3, 5 are excitatory

  • M2, 4 are inhibitory

• M2 receptors help slow heart rate

• atropine (antagonist) blocks muscarinic receptors-dilates pupil

acetylcholine function

• CNS

  • learning and memory

  • widespread loss in Alzheimer’s

• PNS

  • both sympathetic and parasympathetic

  • all striated muscle movement

organophosphates

• insecticides and herbicides

• nerve agents (SLUD: salivation, lacrimation, urination, defecation)

• happens because NT is not removed from synpase

• chemical warfare

amino acid neurotransmitters

• GABA

• glutamate

GABA

major inhibitory amino acid NT

• glycine: major inhibitory NT in spinal cord

• receptors

• GABA_A-ionitropic, fast inhibitory effects

  • chemically gated Cl- channel

• GABA_B-metabotropic, slow inhibitory effects

• target for many anti-anxiety meds and tranquilizers

• reduced expression in prefrontal cortex of schizophrenic patients

glutamate

major excitatory amino acid NT

• depolarization

transmission uses ionotropic receptors (applies to any NT)

• AMPA: NA+ channel

• Kainate: NA+ and K+ channel

• NMDA: Ca++ channel (slowest)

• excitotoxicity: neural injury (like stroke) causes excess release of glutamate, which is toxic to neurons

neuropeptides

small protein neurotransmitters

• often co-released with classical NT’s

• modulating effect

• released in all parts of axon terminal, not just active zone

• destroyed by enzymes after release

• most receptors are metabotropic

• endorphins: endogenous opioid peptides (analgesia and reward)

nitric oxide

• differs from other NT’s

• produced in locations other than axon terminals (mainly in dendrites and diffuses as soon as it’s produced)

• retrograde transmitter: diffuses back into presynpatic neuron

• activates 2nd messenger pathways

• modulates activity of other NT’s

monoamines

• serotonin

• dopamine

• norepinephrine

dopamine

• involved in movement, attention, motivation, learning, reinforcement

• reward seeking vs reward enjoyment

• all metabotropic

• DA dysfunction associated with Parkinson’s disease, schizophrenia, autism, ADHD

• mesolimbocortical pathway: ventral gemental area to nucleus, accumbens, cortex, and hippocampus (reward + reinforcement)

• mesotriatal pathway: substania nigra to striatum (basal ganglia; important for movement; reduced in Parkinson’s disease deep brain stimulation)

serotonin (5-hydroxytryptamine)

regulation of:

• mood

• social behavior

• appetite

• sleep

~20 5-HT receptors

ssri (selective _______ reuptake inhibitors)

endogenous

NT receptor closed or open (with transmitter)

exogenous

drug/agonist (open)

antagonist (closed)

non-competitive antagonist (transmitter binds but closed)

signaling changes receptor expression

neurons down-regulate in response to agonsit drug (fewer available receptors)

neurons up-regulate receptors in response to an antagonist

what did Berthold’s experiment demostrate about hormones?

a hormone released from the testes (testosterone) must be present early in life to have dramatic effects on the body and behavior

hormone

chemical secreted by a gland that travels through the bloodstream and regulates target organs and tissues

• testosterone

• estradiol

endocrine

communication via the circulatory system

endocrine glands

release hormones within the body

• pineal gland

• pituitary gland

• adrenal gland

exocrine glands

use ducts to secrete fluids outside the body

• salivary gland or sweat glands

neurotransmitters

• travel short distances

• precise destination

• high concentration reaches target cell

• rapid effects (ms)

hormones

• travel long distances through the blood stream

• spread throughout the body

• low concentration reaches target cell

  • receptors have extremely high affinity

• slower effects (s, mins)

protein hormone/peptide hormone

a string of amino acids

• G-coupled protein receptor

• typical action is through a 2nd messenger

• sec-min

amine hormones/monoamine hormones

modified amino acids

• G-coupled protein receptor

• typical action is through a second messenger

• sec-min

steroid hormones

four rings of carbon atoms (derivatives of cholesterol)

• typical action is to bind DNA and act as a transcription factor

• alter gene expression

• hrs-days

• similar structures, selective receptors

• partial enzymatic pathway

hypothalamus

hormone regulation

controls hormone secretions

pineal gland

reproductive maturation; bodily rhythms

pituitary gland:

• anterior pituitary

• posterior pituitary

• hormone secretion by thyroid, adrenal cortex, and gonads; growth

• water balance; salt balance

thyroid

growth and development; metabolic rate

adrenal glands:

• adrenal cortex (outer bark)

• adrenal medulla (inner core)

• salt and carbohydrate metabolism; inflammatory reactions

• emotional arousal

pancreas

sugar metabolism

gut

digestion and appetite control

gonads (testes/ovaries)

body development; maintenance of reproductive organs in adults

sexual behavior/development

AVPV

• uptick by fat tissue

• regulate puberty

• when active, especially for women, puberty begins

growth

James matthew barrie

• short stature has been attributed speculatively to childhood emotional distress

• psychogenic dwarfism (potentially)

• trauma → reduced growth hormone

endocrine feedback loops (homeostasis)

• too little X is detected (hypothalamus)

• hormone Y is released (endocrine cells to target cells)

• hormone Y increases X (biological response)

• as X rises, hormone Y release decreases (back to beginning)

• negative feedback

vasopressin hormone feedback loop (water retention)

blood becomes too concentrated

• hypothalamic osmoreceptors detect increased osmolarity

vasopressin is released

• the posterior pituitary releases vasopressin into the bloodstream

kidneys conserve water

• vasopressin increaases water reabsorption, reducing water loss in urine

negative feedback reduces release

• retained water lowers blood osmolarity, reducing vasopressin secretion

monogamous brain

vasopressin → monogamous

over expression → not monogamous

neuroendocrine communication

• neuroendocrine cells blend neural and endocrine communication

• receive NT signals, integrate PSPs, fire action potentials

• release hormones (action potential) into the bloodstream (target cell)

• ex: neuroendocrine cells in the hypothalamus

brain structure and function are modified for an animal’s specific needs

• rats have a larger S1 (olfactory)

• squirrels have a larger V1 (vision)

rat barrel cortex

rats use whiskers to navigate the dark and devote a large amount of cortex to processing sensory info from whiskers (each whisker corresponds to a sensory signal)

brain differences support behavior differences

food-storing species of birds have twice as large a hippocampus in relation to their forebrain (telencephalon) as do species that do not store food

• hippocampus → memory

the social brain hypothesis

the average size of social groups is directly correlated with the size of the cortex

• support social interaction

• sociality drives human brain evolution/expansion

• prosimians<monkeys<humans

what was Haeckel known for?

ontogeny recapitulates phylogeny

• turned out to be fraud

ectoderm

thickens and folds to form neurulation (nerual tube)

growth and initial differentiation

designation of initial brain regions

begins (primary vesicles)

notochord

initiates neurulation and eventually becomes the vertebra

neural crest cells

become PNS

neural tube

becomes CNS

• anterior end: brain

• posterior end: spinal cord

human brain weight as a function of age

most rapid from 0-10 years of age

• neuron growth

• dendritic branching

• synapse formation

• myelination

• new glial cells

• you are born with most of your neurons

peaks then goes downhill at around 20 years of age

the 6 stages of neural development

1. proliferation

2. migration

3. differentiation

4. synaptogenesis

5. cell death

6. rearrangement

proliferation of neurons and glial cells

• V: ventricular zone

• M: marginal zone

• I: intermediate zone

• VM, VIM

• the cortex develops inside out

• thickening of neural tube wall

• neuronal precursor cells migrate by extending a process and then moving the nucleus towards the surface of the brain

• some of these cells return to the ventricular zone to divide again

• 
  

migration

• migrating cells climb along radial glia

differentiation

the fate of a specific cell depends on both its genetic program and the chemical signals it gets from its surroundings

• chemical signals affect gene expression to make the protein that different cell types need

• some genes are down regulated

• some genes are up regulated

• leads to adult phenotype (neurons)

example Sonic hedgehog:

• many TFs, overlapping and reused

• some cells become motor neurons (develop machinery to make acetylcholine, extend axons towards muscles)

• main idea: different combinations of shared and cell type-specific transcription factors regulate gene expression during development, giving rise to the remarkable diversity of neurons in the brain

example axon targeting:

• each cell in retina has certain amounts of ephrin

• optic tectum or thalamus

early development of cortex

dendrites and axons grow extensively

after birth, there is a rapid increase in the number of synpases

postnatal development of synapses

birth to 1 year → over production of cells and synapses

ages 1-5 → call away cells and neurons that are not useful (cell death, synaptic pruning)

• active synapses survive pruning as connections are strengthened

how neural circuits form?

neuromuscular junction

• motor neurons compete for territory for muscle fiber

• the strength comes from NGF

• 1 motor neuron per muscle fiber

• cell death/synapse removal → Rita Levi-Montalcini

Rita Levi-Montalcini

identified nerve growth factor as the substance that promoted neuron growth and cell survival

• requires successful access to target-derived trophic factors

• NGFs promote cell survival

death genes regulate apoptosis

diablo → pro-death gene

Bcl-2 → pro life gene

caspases → protein-destroying enzymes (normally inhibited by IAPs)

1. high levels of Ca2+ enter the cell

2. diable is released from the mitochondria and inhibits IAPs (inhibitors of apoptosis proteins)

3. caspases destroy proteins and DNA of the cell

4. cell death

synaptic remodeling in the developing human brain

involves thinning of neocortex as synapses are retracted

one of the last areas to fully mature is the prefrontal cortex

touch

an interpretation of reality

the brain interprets sensory activity based partly on the body’s usual organization

perception can conflict with physical reality when sensory info comes in an unusual configuration

change blindness

we are not aware of most sensory info