Physiological Psych 1-4

The Neuron Doctrine (Cajal)

the brain is made of individual cells that communicate at points of near contact (synapses) but are not a continuous nerve net (the reticular theory championed by Golgi). Not proven until the invention of the electron microscope in the 1950s

Neuron

fundamental unit of the brain.composed of a cell body, receptive extension dendrite, and a transmitting extension (80-90 billion neurons in the adult human brain). specialized cells to perform integrative info processing. Compared to other cells, neurons have a lot of rough ER, mitochondria, and cytoskeletal structures; They are made up of proteins that are encoded by DNA in the nucleus

Cell body or soma

bulging central region. defined by cell nucleus

Axons and dendrites

radiating processes; one axon and many dendrites; Information flows in one direction from the dendrites through the cell body and down the axon to the axon terminal

Input zone

where neurons collect and process information, either from the environment and other cells; cell body and dendrites

Integration zone

where the decision to produce a neural signal is made (or axon hillock)

Conduction zone

where information can be electrically transmitted over great distances; axon

Output zone

where the neuron transfers info to other cells; axon terminals

Dendrites

trees located with a lot of branches (arborization); spines have many receptors that respond to neurotransmitters; Think of them like antennae tuned to respond to specific patterns of input. Most synaptic connections occur at dendritic spines, synapses primarily located there; They add up/summate all the presynaptic inputs

Axons

one per neuron, through branching collaterals mean there can be multiple post-synaptic targets. Axon begins at the hillock, ends at terminals. Synapses occur at the terminals OR at swollen regions along the axon’s length, known as en passant boutons

Synapses

physical gaps or spaces between neurons (synaptic cleft); many per neuron. Pre- and post- synaptic components; electrical (action potential) and chemical (neurotransmitter) forms. ; Primary release site of neurotransmitters (pre-synaptic terminals) through action potential; Location of many receptors (post-synaptic spine)

Pre-synaptic neuron

sending neuron (axons); region of a synapse that releases neurotransmitters

Post-synaptic neuron

receiving neuron (dendrites); region of a synapse that receives and responds to neurotransmitter

Glial Cells

provide structural, nutritional, and other types of support to the brain

Astrocytes

elaborate processes with a star-like appearance; maintain appropriate chemical environment for signaling; help maintain the blood brain barrier (BBB). Regulate chemicals in the extracellular space, often closely associated with synapses. Regulate extracellular potassium levels. buffer/regulate neurotransmitters, may even release some neurotransmitters and regulate synaptic activity

Oligodendrocyte

wraps axons with fatty myelin (white matter) in the CNS, which insulates axons and increases the speed of action potentials. Schwann cells do the same thing in the PNS

Microglial cells

“immune cells” of the brain; scavenger cells that remove cellular debris. Moderate local brain inflammation and fight infection. Can influence neuronal survival/death

Neurophysiology

branch of neuroscience that studies the electrical functioning of neurons

Calcium imaging

way to investigate activity of neurons

Axon terminals

swellings at the end of the axon that form a synapse and transmit the neuron’s signals to other cells

Presynaptic membrane

specialized membrane of the axon terminal of the neuron that transmits info by releasing neurotransmitters

Synaptic cleft

space between presynaptic and postsynaptic membranes

Postsynaptic membrane

specialized membrane on the surface of the cell that receives info by responding to neurotransmitter from a presynaptic neuron

Nissl stains

cell stains that outline cell bodies in a sample of tissue because the dye is attracted to RNA distributed within the cells; allow us to measure the size and number of cells in particular regions

Golgi stains

label only small number of neurons in a sample, but very completely and reveal fine details of cell structure

Axon hillock

cone-shaped area from which axon originates out of the cell body; where info arriving from all synapses is collected and integrated. Determines when the neuron will produce neural signals of its own, encoded info in a stream of electrical impulses that race down the axon

Innervate

to provide neural input

Dendritic spines

increase the surface area of the dendrites and allow for extra synaptic contacts, may rapidly be altered in both number and structure by experience

Myelination

process of ensheathing axons in myelin. Increases the speed that electrical signals pass down the axons

Myelin

fatty insulation around an axon, formed by glial cells, that speeds the conduction of action potentials

Nodes of Ranvier

gap between successive segments of the myelin sheath where the axon membrane is exposed

Multiple sclerosis

disorder characterized by widespread degeneration of myelin

Cytoarchitecture

cellular layer/composition of the CNS. Cytoarchitecture of the brain is very complex and very small; observations must be made at a microscopic level. Macro-scale structure tells us little about the fundamental parts and microscopes weren't invented until the 1620s

Neurophysiology

branch of neuroscience that studies the electrical functioning of neurons

Peripheral nervous system

all nervous system parts outside the skull and spinal column

Central nervous system

brain and spinal cord

Gyri

ridged or raised portion of a convoluted brain surface, created by folding of cortex; greatly increases the amount of cortex that can fit inside the skull

Sulci

furrow of a convoluted brain surface, separate the gyri; greatly increases the amount of cortex that can fit inside the skull

Gray matter

portion of the brain that is dominated by cell bodies and is devoid of myelin; primarily receives and processes information

White matter

consists largely of axons with white myelin sheaths; mostly transmits info

Corpus callosum

main c-shaped band of axons between the two cerebral hemispheres that allow the brain to act as a single entity during complex processing

Frontal lobe

anterior of the cerebral cortex; important for movement planning, high-level cognition, rationale, cognitive executive functions, planning, movement

Parietal

between front and occipital lobes of each cerebral hemisphere; receive sensory information from the body (especially somatic), participate in spatial cognition

Temporal

below parietal and frontal lobes; receive auditory information and participate in sense of smell, learning and memory (implicated by hippocampus, which is located here)

Occipital

back of the brain, specialized for visual processing

Thalamus

relay station for sensory information and motor signals from the PNS, also plays a role in sleep and alertness

Hippocampus

critical for some forms of learning and memory

Amygdala

plays important role in memory, decision-making, and emotional responses (especially fear, fear learning, anxiety, and aggression). Highly implicated in PTSD

Cingulate gyrus

involved in emotions; implicated in direction of attention

Limbic system

group of brain nuclei that are critical for emotion and learning

Thalamus

surround third ventricle and direct almost all incoming sensory input to appropriate regions of cortex for processing

Hypothalamus

ventral to the thalamus; plays role in hunger, thirst, temperature regulation, sex, etc; controls pituitary gland and serves as brain’s main control for hormonal systems

Ions

atom or molecule that has acquired an electrical charge by gaining or losing one or more electrons

Anions

negatively charged ion, such as a protein or chloride ion

Cations

positively charged ions, like potassium or sodium

Intracellular fluid

cytoplasm; watery solution found within cells

Extracellular

fluid in the spaces between cells and in the vascular system

Cell membrane

separates extracellular and intracellular fluid; all living cells are more negative on the inside than the outside

Monovalent

one bond; Na+, Cl-, K+

Diavalent

two bonds; Ca2+, Mg2+

Phospholipid Bilayer/Membrane

naturally combine to form a stable bilayer with hydrophilic heads facing the exterior and hydrophobic tails on the interior, away from water

Hydrophilic compounds

dissolve in water due to uneven electrical charge (e.g. salt)

Hydrophobic compounds

do not dissolve in water due to even electrical charge (e.g. oils)

Lipids (fatty acids) are hydrophobic

contribute to resting state and action potentials by forming a barrier

Resting membrane potential (RMP)

difference in electrical potential across the membrane of a neuron during an inactive period, established by ionic concentration gradients; about -50 to -80 mV

Glutamate

small amino acid neurotransmitter and the primary excitatory neurotransmitter of the brain; glutamatergic (using glutamate) projections are widespread and found through the CNS

Excitotoxicity

a phenomenon caused by excessive glutamate activity in which a stroke or physical trauma provokes excessive release of glutamate that overexcites neurons, eventually killing them (induced apoptosis)

Three types of glutamate receptors

AMPA, NMDA, Kainate. All competitive agonists of their respective receptors, they all mimic the effects of glutamate, and all ionotropic

Neuropharmacology of glutamate receptors

An action potential causes glutamate release -> binds to AMPARs and NMDARs. Influx of Na+ through AMPARs and Na+/Ca2+ through NMDARs causes an EPSP in the postsynaptic neuron (depolarization). NMDARs only allow ion flux when the membrane is already depolarized

Signaling termination

excess glutamate is taken up by astrocytes and recycled. Glutamate in the synapse is taken up by transporter proteins on nearby astrocytes, converted to glutamine, and transported back into the presynaptic neuron where it is turned back into glutamate and recycled. This presynaptic process terminates the excitatory action of the glutamate in the synapse

Acetylcholine (ACh)

anime neurotransmitter that is synthesized at the base of the frontal cortex and brainstem, and cholinergic (using acetylcholine) projections are widespread through the CNS and PNS. First neurotransmitter discovered (Otto Loewi) and first thing that changes in the brain when you wake up is start up of cholinergic activity. Important for muscle contractions (PNS), learning and memory, attention and arousal (CNS)

Two major ACh receptors

Nicotinic AchRs and Muscarinic AchRs

Nicotine

IONOTROPIC competitive agonist from the tobacco plant that causes skeletal muscle to contract, no effect on the heart, nAchRs mostly found in skeletal muscle. Very rapid and usually have an excitatory effect.

Muscarine

METABOTROPIC competitive agonist from some mushroom species has little effect on skeletal muscle, but slows heart rate considerably (dangerous!), mAchRs mostly found in heart muscle. Uses G-coupled protein receptors, which have slower and responses and may be inhibitory or excitatory

acetylcholinesterase (AChE)

enzyme that breaks down excess ACh in the synaptic cleft

GABA

amino acid neurotransmitter and the primary inhibitory neurotransmitter of the brain. GABAergic neurons are widespread, and found throughout the CNS. GABA fine-tunes activity in local circuits and plays an important role in the control of anxiety, mood, and arousal. provides balance in the brain.

Three major GABA receptors

GABA-A (ionotropic), GABA-B (metabotropic), GABA-C (ionotropic)

GABA-A (ionotropic)

fast inhibitory neurotransmission, lets chloride ions in and hyperpolarizes, causing an inhibitory postsynaptic potential

GABA reuptake/signaling transmission

Excess GABA in the synaptic cleft is reabsorbed into the presynaptic terminal by the action of GABA transporters (GAT) where it is recycled back into synaptic vesicles for re-release

Nervous System Balance

needs a balance between excitation (GLU) and inhibition (GABA) -> too much inhibition causes the brain to shut down and too little leads to epilepsy or seizures

Benzos, barbiturates, and ethanol

potent sedatives (noncompetitive because they bind to their own separate sites) to increase the probably that the channel opens when GABA binds and/or keep the channel open longer. Alcohol (ethanol) inhibits neurons that are responsible for controlling behavior

Receptor rule

Each receptor binds a single neurotransmitter type, but a given neurotransmitter type can often bind to multiple receptor types

Neuropharmacology

Concerned with discovery and study of compounds that affect the nervous system and behavior

Ionotropic/ligand gated

transmitter-gated ion channel (directly). Neurotransmitter binds directly to the channel protein -> channel opens immediately -> ions flow across membrane for a brief time. Extremely fast/instantaneous response

Physical ‘gating’ properties of the receptor channel determine which ions are allowed to flow (sometimes several)

Metabotropic

G-protein coupled receptors (indirectly). Neurotransmitter binds g protein-coupled receptor -> g protein activated -> g protein affects g protein ions or receptors or whatever. GPCRs are slower, but usually result in a strong signal (larger depolarization) due to signal amplification, more ion channels activated

The effect of a neurotransmitter on a neuron depends

on the receptors expressed, membrane voltage, and ion concentration

Summation

allows the post-synaptic neuron to in integrate the electrical information provided by all inhibitory and all excitatory synapses acting on it at any given moment

dendritic receptors

may be either inhibitory or excitatory; ionotropic or metabotropic. depolarization decreases as a function of distance (passive conductance) unlike axons, because there is no myelination in the dendrites or in the cell body. There is passive current leakage

Effects of neurotransmitters are defined by the receptor

Depolarization (EPSP) -> Excitatory (e.g. Glutamate); sodium. Hyperpolarization (IPSP) -> Inhibitory (GABA), Chloride

Receptors

proteins on cell surfaces or within cells

Ligand

molecule that binds to a receptor with some selectivity. A ligand can either activate the receptor or block the receptor. e.g. a neurotransmitter or a drug

Agonist

molecule (e.g. a drug) that binds to receptors to initiate or enhance a response

Antagonist

molecule that binds to receptors and blocks or reduces the action of a neurotransmitter

Competitive agonist

binds to receptors at the same location as the neurotransmitter, activating it. NT and drug compete for receptor

Competitive antagonist

binds to receptors at the same location as the neurotransmitter to block/reduce its action

Noncompetitive agonist

binds to receptors at a different location as the neurotransmitter, activating/enhancing its activity

Noncompetitive antagonist

binds to receptors at a different location as the neurotransmitter, blocking/reducing its activity. GABA receptors are noncompetitive

Agonist and Antagonist Receptor Interactions

Agonist + receptor = drug action/effect; Initiates or enhances receptor activity. Antagonist + receptor = no drug action/effect; Blocks or reduces receptor activity

Bioavailability

proportion of substance/drug consumed that becomes completely available to its intended biological target

Blood Brain barrier

highly selective, semi-permeable border of cells that prevents substances in the circulating blood from crossing into the CNS (where neurons reside). Endothelial cells (and astrocytes) provide a solid lipid barrier with no gaps, so that non-lipid soluble substances cannot get into the brain. Protects the brain from foreign pathogens, toxins, etc.