Neuro vocab weeks 6-9

What are the 3 opioid receptor subtypes

mu, kappa, delta

Periaqueductal gray

brainstem structure that is a key area for opioids’ pain relieving (analgesic) effects

mu receptors

receptor in ventral tegmental area (VTA), play a role in opioid addiction

• located on GABA interneurons in VTA

• open receptor, stopes GABA so dopamine neuron goes..

Key component of Marijuana/CBD

THC (delta-9-tetrahydrocannabinol)

Endocannabinoids, anandamide, and 2-AG

Released postsynaptically by activated synapses and then bind to receptors on presynaptic side (retrograde signals)

Cannabinoid receptors CB1 (brain) and CB2 (immune system)

Both GPCRs, activation slows the release of neurotransmitter from the presynaptic side

• effects on memory, cognition

Cannabidiol (CBD)

Found in marijuana, effects are less understood

• may have antagonist effects

• FDA approved for treating epilepsies

• may blunt the psychoactive effects of THC

Stimulants

Have an excitatory effect on the nervous system

Nicotine

Causes rewarding effects dur to nACh-Rs in ventral tegmental area (VTA)

• highly addictive

• peripheral effects are mediated by actions on nACh-Rs at nerve-muscle junctions

Cocaine

made from purified coca plant leaves

• blocks biogenic amine transporters, DAT but also sometimes NET and SERT

• blocks reuptake

• effects depend on action potential stimulated release of DA

• highly addictive

Amphetamine stimulants

Amphetamine, methampetamine, methylphenidate (Ritalin), adderall

• amphetamines reverse DAT activity, so not dependent on action potential stimulated release of DA like cocaine, but they dump DA into the synapse

Hallucinogens

LSD, psilocybin, mescaline

(sometimes PCP and ketamine as well)

Effects of hallucinogens

Occur via activation of the 5-HT-2A receptor, in visual cortical areas or in the occipital lobe

Effects of PCP and ketamine

• sometimes classified with hallucinogens, very different mechanism

• produce a dissociative state from NMDA-R (GluR)

• small doses can be used as an anesthetic or to relieve depressive illness

Metabolic tolerance

body’s metabolism and organs (liver especially) become increasingly better at clearing the drug

Functional tolerance

Brain shows less sensitivity to drug over time

Down regulation

decrease in receptor number and/or sensitivity in the case of metabotropic receptors

• may occur in response to repeated agonist administration

Up-regulation

increase in receptor number and/or sensitivity

• may occur in response to repeated antagonist administration

Cross tolerance

tolerance that generalizes to other drugs in the same chemical class

• (ex heroin has cross tolerance with other opioids)

Opponent-process model

(models for studying addiction)

• Drug addiction is a result of pairing physiological/emotional pleasure and the physiological/emotional symptoms associated with withdrawal

• Over time, pleasure decreases, and withdrawal symptoms become more prominent

Evolution

Gradual changing of one species into another

• indifferent process regardless if helpful or harmful

4 observations of evolution

1. Reproduction increases population size unless factors limit it

2. Individuals in a species are not identical

3. Some variation among individuals is due to inheritance

4. Not all offspring survive to reproduce

Natural Selection

process where traits become more or less common based upon differential reproduction over time

Adaptations

traits which increase the probability of survival of the organism/species

Fitness

Refers to how well a species or member of the species ‘fits’ into its niche

Homology

Features based on common ancestry

Homoplasy

Similar features that evolved separately

Analogy

biological traits or structures that perform the same function in different species but evolved independently without a shared ancestral origin

• via convergent evolution

How many chromosome pairs do genes/DNA have

23 pairs

Taxonomy

Describing, identifying, naming, and classifying organisms into structured hierarchical groups

Phylogeny

The study of the evolutionary history and relationships among groups of organisms

Basic similarities in nervous systems across ALL vertabrates

• development from a hollow dorsal tube

• bilateral symmetry

• segmentation

• hierarchical control

• separate systems

• localization of functions

—brain structures are basically all the same in vertebrates, except for the cortex

—humans have small olfactory bulb and large cortex

Encephalization quotent (EQ)

Takes into account each class’s deviation from the slope of the ratio of brain weight to body weight for all species

How many layers are in the neocortex

six

How many layers are in the allocortex

four

Australopithecus

• first appeared 4 million years ago

• bipedal (upright) hominin

• made stone tools

• tool making ability reduced selective pressure for large jaws and teeth

• prominent for social harmony in society, weapons caused threat

Homo species (general)

Appeared in the last 2 million years

• brain volume reached plateau at this time

• comes after Australopithecus

Homo habilis

• had cerebral volume of 600-700 cm3

• first of homo species

Homo erectus

• had cerebral volume of 700-1400 cm3

• (expanded over a 1.5 million year period)

• 2nd of homo species

• used fire, tools, killed large animals

• spread over asia, africa, europe

• lived 40 thousand years ago

Homo sapiens

• Emerged 150,000 years ago

• Cerebral volume of 1400 cm3

Social Brain Hypothesis

Humans evolved large brains to navigate complex social relationships and group dynamics, rather than to solve purely ecological problems

Sexual selection hypothesis

Traits evolve because they increase an individual's success in getting mates, even if those traits reduce individual survival

• By Charles Darwin

• other possibilities: tool use, social learning, etc

Genotype

An organism's complete set of genetic material or the specific genetic makeup (DNA sequence) inherited from its parents

• contained within an individual

Phenotype

An organism's observable characteristics and traits:

• height, eye color, hair color, blood type, behavior, and disease presence

Ectoderm

• outer layer of zygote that is formed during gastrulation

• part of it becomes the nervous system, the rest of it becomes skin

Gastrulation

Formation of the germ layers: single layered blastula into a multi-layer embryo

• ectoderm

• mesoderm

• endoderm

Transcription factors

Proteins that bind DNA and switch genes on or off

• Act in cascades; they establish the body plan (segmentation) and then the specific cell types and tissues within it.

• ancient machinery that is shared across many species

• Ex: Homeotic (Hox) genes

Neural tube

• Precursor of the ventricular system

• Result of the dorsal surface thickening; surrounds a fluid-filled cavity

• Anterior end enlarges and differentiates into the hindbrain, midbrain, and forebrain

• The rest of the neural tube becomes the spinal cord

6 stages of neural development

1. neurogenesis

2. cell migration

3. differentiation

4. synaptogenesis

5. neuronal cell death

6. synaptic rearrangement

• stages can overlap across and within regions

Neurogenesis

New, functional neurons are generated from neural stem and progenitor cells

• cells on inner side (VZ) of neural tube undergo cell division

• cells in VZ provide source where all neurons and glial cells are derived

• increase in brain size is due to cell growth, myelenation, glial cell production, etc

• continues to occue in a very limited capacity in some brain regions through adulthood

• the extent this goes in humans is actively debated

Ventricular zone (VZ)

Temporary embryonic layer of tissue that lines the neural tube in developing embryos

Olfactory bulb

Located on the bottom side of the forebrain, resting just above the nasal cavity and roughly between the eyes

• very prominent in rodents, not so much in humans

• processing smells

Granule neurons

Small, densely packed neurons found primarily in the cerebellum and the dentate gyrus of the hippocampus

• continue to undergo replacement through adulthood

Dentate gyrus

Narrow strip of gray matter in the temporal lobe that forms part of the hippocampal formation

Cell migration

Movement of newly formed neurons and glia to their eventual locations, there are 2 types:

• radial migration

• tangential migration

Complete before birth, except some interneurons may keep migrating in the frontal cortex for a few months

• When this fails: “smooth brain” occurs; neurons never reach their layers, causing severe intellectual delays

Radial migration

Neurons move outward from the inner ventricular zone (VZ) toward the outer surface of the developing neural tube or cerebral cortex.

• occurs on “scaffolding cells”

• radial glia from the VZ toward the out surface

• ex: pyramidal neurons

• vertical

Tangential migration

Involves the movement parallel to the brain’s surface, along the axis of the nervous system

• allows neurons to travel horizontally over long distances to their final destinations

Radial glia

Long cells that allow neurons to migrate along them like a highway

Cell differentiation

Unspecialized cells (like stem cells) develop into specialized cells with distinct structures and functions

• before migration

• This allows multicellular organisms to form complex tissues, organs, and systems, as well as repair and replace damaged cells in adults

Neural cell adhesion molecules (NCAMs)

Proteins on the outer surface of cells that guide cells growing axons to their targets

• Just one example of the many important molecules for guiding neuronal processes to their correct location

Growth cones

tips of growing axons

• contain finger-like extensions

• filopodia at their tips detect local chemicals in the environment

Filopodia

thin, finger-like membrane extensions that project from the leading edge of a developing axon

chemoattractants and chemorepellents

chemical signals that guide growing neurons to their correct targets by directing the growth cone

Synaptogenesis

the formation of the synaptic connections between neurons during brain development

• occurs throughout life as neurons are constantly forming new connections and discarding old ones

• but slows over time

Apoptosis

“programmed” cell death

• gene expression-dependent

Necrosis

Cell death from injury or damage

• trauma or disease

Neurotrophins

• provided by postsynaptic targets

• necessary for presynaptic cells to survive

• if they dont recieve enough, they die

• allow for matching between the size of target and the number of neurons with axonal efferents to the target region

Nerve growth factor (NGF)

A neurotrophin secreted into target organs (ex muscles) in the peripheral nervous system

• regulates the growth, maintenance, survival, and differentiation of specific sympathetic and sensory neurons

Brain-derived neurotrophic factor (BDNF)

a key neurotrophin secreted by target neurons in the neocortex and the hippocampus

• A protein that promotes the survival, growth, and maintenance of neurons (nerve cells) in the brain and spinal cord

• Low BDNF levels are often associated with conditions like depression, Alzheimer’s disease, and Parkinson’s disease

Synaptic rearrangement

describes the process where earlier formed synapses may be eliminated, and others added

Gliogenesis

glial cells are generated from neural stem cells and progenitor cells

• occurs throughout prenatal development concurrent with neurogenesis

• increases after birth for many animals, and continues through life

Myelineation

Myelin sheath forms around the axon

• occurs primarily after birth

• very important for increasing AP velocity (good for cognitive functioning)

Behavioral teratology

Study of how maternal environment influences the nervous system in the fetus

• ex: pre or postnatal exposure to toxins, drugs, or other environmental disturbances

Teratogen

Any substance, agent, or environmental factor that can disrupt normal fetal development and cause permanent birth defects

• e.g., Accutane, alcohol

Transgenic model

An animal (usually a mouse) with the artificial introduction or removal of a gene

• knockout, knock-in, over-expression mutant

Knockout (KO)

A specific gene is inactivated or removed in an animal model

Overexpression mutant

increase expression of an existing gene by inserting extra copies of it into the DNA

Conditional knockout

Expression may be targeted into certain cell types in the body, or its KO is present in the DNA but it is not active until a desired time during a certain time during development

Epigenetics

The study of how your behaviors, lifestyle, and environment can cause changes that affect how your genes work, without altering your underlying DNA sequence

• ex: during early life (pre/postnatally), experience can change the expression pattern of genes; this can have long-lasting effects

DNA methylation

Chemical modification of parts of the genome usually prevents gene expression at that site

• A natural cellular process where tiny chemical tags called methyl groups attach directly to a DNA molecule without changing the underlying genetic code

• Methyl groups act as light switches, turning genes on and off

Histone modification

Alteration of histone proteins

• Proteins act as a “spool” for chromosomal DNA, and control how tightly or loosely the DNA is packed

Autism spectrum disorder (ASD)

• a class of disorders of neural development characterized by impaired social interaction/communication and restricted interests and repetitive behavior

• Signs usually evident by 3 years old, diagnosis often later

• Causes are not understood, but clear genetic component

• Abnormal development of interneurons in the cerebral cortex

Attention deficit/hyperactivity disorder (ADHD)

• symptoms present before age 12

• complex genetic and environmental causes that are not yet well understood

• some differences noted in the prefrontal cortex

• diagnosis rates have risen over time

Law of specific nerve energies

Specific receptors and neural channels for each sense are independent

• each can only produce one specific sensation

• they all encode information in terms of firing APs to the brain

Adequate stimulus

The specific type of energy that a sensory organ/receptor is most sensitive to

ex: photon of light for an eye, soundwave for the ear, chemical for taste/smell

Transduction

Conversion of physical energy by a receptor into an electrochemical pattern in neurons

Generator potentials

• very similar to EPSPs

• When large enough threshold, these trigger an AP in the sensory neuron

Topography

Neighboring points on a sensory or motor surface correspond to neighboring neurons in the brain or spinal cord

Coding in sensory systems

Neural activity patterns that simplify and represent information for efficient transmission

Rate coding

How many APs per second

• encodes stimulus intensity

• more APs = stronger stimulus

Labeled line coding

Neurological model where each individual sensory receptor or nerve fiber is specialized to respond to one specific type of stimulus

• Information about each quality travels to the CNS on its own afferent pathway

Somatosensation

Sense of touch

• detection of body sensations (touch and pain)

• stimulus location is determined from the position of the activated receptors, the somatosensory inputs map onto a representation of the body’s surface in the cerebral cortex

Pacinian corpuscle

Exemplar touch receptor

• detects sudden displacement or high-frequency vibrations on the skin

• onion-like outer structure

• vibrations increase the flow of Na+ to trigger an AP

Adaptation

the progressive loss of a response to a maintained stimulus

• key for representing changes in one’s environment, with no adaptation we are constantly bombarded with meaningless info

Tonic receptors

Show slow or no decline in AP frequency

Phasic receptors

display adaptation and decrease frequency of APs

Receptive field

Specific region of the skin, muscle, or internal organ where a stimulus must occur to change the firing rate of a sensory neuron

• bullseye pattern

• On-center and Off-surround

• cat diagram

Primary somatosensory cortex (S1)

Receives touch information from one side (the opposite) of the body