Behavioral Neuroscience Test 1

get a hint

hint

Mentalism

Mentalism

~ Originated in Ancient Greece

~ Believed the mind (psyche) is the source of all human behavior (consciousness, perceptions, emotions, imaginations, opinions, desires, etc etc)

~ Psyche was considered a nonmaterial identity independent of the body

~ Largely attributed to Aristotle

Dualism

~ Originated with Descartes

~ Suggested that the nonmaterial mind resides in the pineal gland and is separate from the body, but the mind and body “must be conjoined to constitute people,” and that the mind controls the body via the pineal gland and the use of the ventricles (and their CSF)

~ Criticized for not being able to reconcile the mind-body problem - what is the mechanism for a nonmaterial mind and a physical body to interact?

~ Ran into more issues when people had issues with brain damage to the pineal gland but could still function in ways the theory would deem impossible

Materialism

~ Originated in the mid-nineteenth century with theories of evolution

~ Believes all being, processes, and phenomena can be explained as manifestations of physical matter - it’s all explained by the structure and function of the nervous system, the brain and the body are not two separate things

~ Contemporary view, but some concepts of the other theories remain

Central Nervous System

The Brain and Spinal Cord

Peripheral Nervous System

All nerves outside outside of the brain and spinal cord

Sympathetic nervous system

Expends energy, part of the autonomic nervous system

Parasympathetic nervous system

Conserves energy, part of the autonomic nervous system

Somatic nervous system

Controls voluntary muscles and conveys sensory info to the CNS

Autonomic Nervous system

~ Sends and receives messages to regulate the autonomic functions of the body (heart rate, BP, respiration, digestion, etc)

~ Includes autonomic ganglia that are innervated by neurons that come from the CNS

~ Divided into two subtypes: Sympathetic and Parasympathetic

Preganglionic Fibers

Come from the CNS and innervate ganglia

Postganglionic fibers

Project from ganglia to rest of body

Sympathetic nervous system

~ Network of nerves that prepares the organs for rigorous activity, “fight or flight”

~ dominant during periods of action

~ increases heart rate, blood pressure, respiration, etc.

~ Comprised of ganglia on the left and right of the spinal cord

Parasympathetic nervous system

~ Facilitates vegetative, nonemergency response, “rest and digest”

~ dominant during our relaxed states

~ decreases functions activated by the other half of the autonomic

~ comprised of long preganglionic axons extending from the spinal cord and short postganglionic fibers that attach to the organs themselves

Somatic nervous system

~ consists of axons conveying messages from the sense organs to the CNS and from the CNS to the muscles

~ Contains the 12 pairs of Cranial Nerves

~ Contains the 31 pairs of spinal nerves

Spinal Nerves

~ Connected at regular intervals along the spinal cord, one member of each pair for each side of the body

~ Each nerve consists of two branches, or roots, with different functions. The dorsal root, which carries sensory info, and the ventral root, which carries motor info.

Spinal Cord

~ Part of the CNS found within the spinal column

~ Communicates with the sense organs and muscles, except those of the head

~ Comprised of grey matter and white matter

~ each segment sends sensory information to the brain and receives motor commands

Grey matter

Located in the center of the spinal cord and densely packed with cell bodies and dendrites

White matter

Composed mostly of myelinated axons that carry information from the grey matter to the brain or other areas of the spinal cord

Ganglion

A cluster of neuron cell bodies, usually outside the CNS

Meninges

three membranes that surround the brain and spinal cord

Dura Matter

Outermost layer of the meninges

Arachnoid Matter

Middle layer of the meninges

Pia Matter

Innermost layer of the meninges

Central Canal

A fluid filled channel in the center of the spinal cord

Ventricles

Four fluid-filled cavities within the brain

Cerebrospinal Fluid (CSF)

~ A clear fluid found within the brain and spinal cord

~ provides “cushioning” for the brain

~ Reservoir of hormones and nutrition for the brain and spinal cord

~ Produced by the filtering of blood via the Choroid Plexus

~ Circulates through the ventricles and emerges through the 4th ventricle into the subarachnoid space to be reabsorbed into the blood

Circle of Willis

A confluence of arteries that can maintain perfusion of the brain even if narrowing or blockage limits flow through one part

Blood Brain Barrier

~ A mechanism that surrounds the brain vasculature and blocks most chemicals from entering, helps block incoming viruses, bacteria, and other harmful material

~ Selectively permeable, but not impermeable. Relatively impermeable to large, electrically charged molecules

~ Active transport is required to pump chemicals from the blood into the brain

~ Incomplete at brain regions like the Area Postrema (“Chemical Trigger Zone”, mechanism for removing substances by vomiting) and the Median Eminence (Mechanism for hormones entering the blood)

Neuron Doctrine

Two Key Ideas

~ Contiguous cells: Neurons and other cells are independent structurally, metabolically, and functionally

~ Information is transmitted from cell to cell across tiny gaps (synapses)

Glia

~ Approximately 50% of cells in the CNS

~ Control local blood flow

~ Help form new synapses

~ Help in dendritic pruning and synapse refinement

~ Recieve synapses from neurons

~ Absorb and release important neurochemicals, including neurotransmitters

~ Generate electrical potentials (from ion flow across their cell membranes)

~ Can engage in mitosis

Projection Neurons

Those whose axons project outside of the brain region where their soma (cell body) resides

Interneurons

Those whose dendrites and axons are completely contained within a single structure

Typical resting membrane potential

~ -50 to -90 mV (most typical around -70)

At Rest

Outside - Many(So much) Sodium(+), Chloride(-), Calcium(+0), Few negative proteins(-), Potassium (+) overall relatively more positive

Inside - Many Potassium (+), negative proteins (-), Few Sodium (+), Chloride (-), Calcium (+), overall relatively more negative

Cell Membrane Permeability

Semi-Permeable, particularly to anything fat-soluble, but basically anything charged goes through an ion channel instead

Sodium-Potassium Pump

~ Energy dependent process that counteracts the Na+ leak (and also the "passive” K+ channels)

~ Moves 3 Na+ out for 2 K+ in

~ Accounts for a large percentage of the total energy requirement for the brain

IPSP

~ Small hyperpolarization in the negative direction, often caused by chloride entering the cell or by potassium leaving the cell

~ Does not cause any action on it’s own, but does temporarily make it harder for the cell to potentially produce an action potential or even an EPSP

EPSP

~ Produces a small, local depolarization in the positive direction, pushing the cell closer to the threshold of having an action potential, but not there yet

~ Often results from positive ions entering the cell, like sodium

Action Potentials

~ Threshold varies

~ All or nothing, do not degrade one they start moving down the axon like graded potentials do

~ Trigger voltage-gated channels

Action Potential - Under Rest

~ Both Sodium and Potassium voltage-gated channels are closed

~ (Sodium has two gates on its ion channel, Gate 1 is voltage sensitive and is pointed outwards, towards the rest of the cell. Gate 2 is not voltage sensitive, and is on the inner side of the cell membrane)

Action Potential - Depolarization

~ A small trickling of sodium channels open up, which then becomes a huge flood of sodium channels opening. Potassium channels are still closed, they tend to be a little lethargic and slower than sodium, but will open shortly thereafter

Action Potential - Repolarization

~ Gate 2 (Non-voltage gated) for sodium is now closed (because of the passage of time/ the passage of sodium through the channel), but the voltage-sensitive gate (Gate 1) is still open (the cell is still depolarized). It is the closing of Gate 2 that stops the cell from continuing to be or always be depolarized. Potassium is still moving out of the cell freely, its gate is slower than sodium’s.

Action Potential - Hyperpolarization

~ As the cell is no longer depolarized, Gate 1 for sodium has now closed, and allowed Gate 2 to freely swing open again. Potassium’s gate is beginning to close, but their lethargy allows extra potassium to leave the cell and hyperpolarize it negatively. Eventually, all voltage-gated channels will close and the cell will be able to return to its normal resting state via the work of the sodium-potassium pump.

Action Potential Origination

~ Action potentials originate in the axon hillock, which itself is densely populated with voltage-gated sodium channels

Absolute Refractory Period

~ No matter what, no matter the stimulus or its strength, you cannot generate another action potential with this neuron during this period of time. The sodium channels are inactive, it’s impossible

~ Voltage-gated sodium channels are open but fully inactive, and voltage-gated potassium channels are closed (on rising phases)

Relative Refractory Period

~ It is possible to generate another action potential during this time, but it is much harder because the cell is currently hyperpolarized

Nodes of Ranvier

~ Open space between myelin for action potential to “jump” to, these areas are full of voltage-gated potassium and sodium channels

Trigeminal Nerve and Lidocaine

~ This nerve has endings all throughout the face and mouth and responds to pressure and inflammation. When there is inflammation or pressure, action potentials are fired and these are interpretated as pain

~ This drug will find voltage-gated sodium channels and block them, preventing sodium from getting into the cell, thus preventing any action potentials from ever firing

Summation

~ A postsynaptic neuron will fire an action potential if a depolarization that exceeds the threshold reaches the axon hillock

Temporal Summation

~ Summing of potentials that arrive at the axon hillock at different times

~ The greater in time they arrive, the greater the summation and possibility of an action potential

Spatial Summation

~ Summing of potentials that come from different parts of the cell

~ The closer the synapses are to the axon hillock, the greater the summation and possibility of an action potential

Axo-Dendritic Synapse

~ Axon of a presynaptic cell connects to a dendrite of the postsynaptic

Axo-somatic Synapse

~ Axon of the presynaptic cell connects to the cell body (soma) of the postsynaptic

Axo-Axonic Synapse

~ Axon of the presynaptic connects to another axon of another presynaptic cell which then connects to the cell body of the postsynaptic

~ This is most common when the presynaptic cells are one that produces IPSPs and one that produces EPSPs, so that the IPSP could potentially inhibit the EPSP one

Dendro-Dendritic Synapse

~ The dendrites of the presynaptic cell connect to the dendrites of the postsynaptic

Electrical Synapse (Gap Junctions)

~ Used for special purposes where very fast, synchronous activity is very important, such as neurons controlling rhythmic breathing

~ Ion channel pores are precisely lined up

~ Represent the vast minority

Classical Neurotransmitters

• Acetylcholine

• Monoamines

  • Catecholamines (Dopamine and Norepinephrine)

  • Indoleamines (Serotonin)

• Amino Acids

  • GABA (Gamma-Aminobutyric Acid)

  • Glutamate

Five Features of a Classical Neurotransmitter

~ Synthesized presynaptically (in the presynaptic terminal)

~ They are packed into vesicles

~ They bind to postsynaptic receptors

~ They are released from released in response to an action potential

~ They must have a mechanism for signal termination

What most directly causes the releasing of neurotransmitters from the vesicles into the synpase?

~ The influx of Ca2+ into the presynaptic terminal as a result of the action potential propagating down the axon

The main methods of signal termination

~ Degradation via enzymes

~ Re-uptake into the presynaptic cell via transporters

~ Simple diffusion

~ The binding of the neurotransmitter to autoreceptors

Ionotropic (Ligand-Gated) Receptors

~ Gated by ligands, do not open unless the ligand causes it to open and undergo a conformational change

~ Two Parts - Binding Site and a Pore (channel)

~ Fast-Acting

~ Represent the minority

Metabotropic (G-protein coupled, GPCR - G protein coupled receptor) Receptors

~ Not an ion channel

~ When the ligand binds, this triggers the release of a g-protein because the receptor undergoes a conformational change

~ Has binding site, but no pore

~ Slower acting

~ Can activate nearby ion channels and/or 2nd messenger proteins

~ The majority

Acetylcholine is synthesized from?

~ Acetyl CoA

and

~ Choline

What packaged Acetylcholine into vesicles?

The vesicular acetylcholine transporter (VAChT)

What are the two types of receptors that react to Acetylcholine?

Nicotinic (Ionotropic) and Muscarinic (Metabotropic) receptors

What enzyme degrades Acetylcholine?

Acetylcholine Esterase (AChE), works very quickly

What is the origin and eventual destination of Acetylcholine?

~ Released by projection neurons that originate in the basal forebrain

~ Projects into most places in the cortex (including the hippocampus)

~ Also released by and into the striatum

Characteristics of all monoamines

~ All have a single amine group (NH)

~ Further divided based on ring structure

~ Includes the Catecholamines and Indolamines

What are the Catecholamines synthesized from?

~ From tyrosine, which itself is synthesized from Phenylalanine

What is tyrosine hydroxylase?

~ The “rate limiting factor” for catecholamines, helps ensure that we have the optimal amount at all times

What is the intermediate protein in the synthesis of dopamine?

~ L-DOPA

~ This is used to treat Parkinson’s, especially because L-DOPA passes the BBB but what it will eventually synthesize into does not

What packages the Catecholamines into vesicles?

~ The vesicular monoamine transporter (VMAT)

What is the precursor to norepinephrine? I.e., what is needed to synthesize NE?

~ Dopamine

~ Via the enzyme Dopamine B-Hydroxylase (DBH)

Where can DBH and Norepinephrine be found?

~ The enzyme is only found in the vesicles

~ The protein can only be synthesized after its precursor protein has been packaged into a vesicle

By what method is the concentration of Catecholamines diminished in the synapse?

~ Reuptake by transporters on the presynaptic terminal via the DA transporter (DAT) and the NE transporter (NET)

What happens to Catecholamines once they are back in the presynaptic terminal?

~ They are degraded by the enzyme monoamine oxidase (MAO)

or

~ Re-packaged into vesicles (via the VMAT) for subsequent release

What are the two main pathways of dopamine?

~ The Mesocortical and the Mesostriatal pathways

What is the origin and the targets of the Mesocortical pathway?

~ Origin = Ventral tegmental area (VTA)

~ Primary target = Nucleus accumbens (NAc), prefrontal cortex, and hippocampus

What is the origin and the primary target of the mesostriatal pathway?

~ Origin = substantia nigra

~ Primary target = striatum

Characteristics of Dopamine receptors

~ Two main families, the D1 family and the D2 family

~ D1 family has D1 and D5

~ D2 family has D2, D3, and D4

~ All of these receptors are metabotropic

What is the origin and primary target of the norepinephrine pathway?

Origin = Locus coeruleus (LC)

Primary targets = Hippocampus, basal ganglia (striatum, Nucleus accumbens (NAc)), prefrontal cortex

Characteristics of norepinephrine receptors

~ Two main families - Alpha and Beta

~ Alpha is A1 and A2

~ Beta is B1 and B2

~ All are metabotropic

What is serotonin synthesized from?

~ tryptophan

what is the rate limiting enzyme of serotonin?

~ tryptophan hydroxylase

What packages Serotonin into vesicles?

~ the VMAT

What is the primary method of signal termination used by serotonin?

~ Reuptake by 5-HT transporter (SERT) located on the presynaptic termnial

What is the origin and primary target of the main serotonin pathway?

~ Origin = dorsal raphe nucleus (DRN)

~ Primary Targets = hippocampus, basal ganglia (striatum, NAc), cortex, thalamus, hypothalamus

Characteristics of serotonin receptors

~ Many different families, with subtypes (over 13 different types)

~ Most are metabotropic

What are the most prevalent neurotransmitters in the brain?

~ Amino Acids

What are the two main types of amino acid neurotransmitters?

~ Glutamate (Glu) which is excitatory

~ GABA which is inhibitory

What packages the amino acids into vesicles?

~ VLGUT - vesicular GLU transporter

~ VGAT - vesicular GABA transporter

What is/are the primary methods for signal termination for amino acids?

~ Reuptake by transporters located on the presynaptic terminal or on nearby glial cells

Where are GLU and GABA containing neurons found in the brain?

Essentially everywhere, GLU only has projection neurons but GABA has both projection neurons and interneurons

What are the ionotropic receptors of Glutamate?

~ NMDA, AMPA, and kainate

~ These ion channels are permeable to Sodium (all 3 above) and/or Calcium (Ca2+) (just NMDA)

~ Activation leads to EPSPs

What are the metabotropic receptors of Glutamate?

~ 8 different types of these receptors

~ This binding leads to the activation of nearby ion channels and/or 2nd messengers

What are the ionotropic receptors of GABA?

~ GABAa receptor, has many ligand spots on it, not only for GABA but also for other ligands such as barbiturates and benzodiazepines

~ Permeable to Chlorine (Cl-)

What are the metabotropic receptors of GABA?

~ GABAb receptor

What are peptides synthesized from?

~ synthesized from the cleavage of proteins (propeptides) in the cell body

~ large and diverse class of chemicals that are proteins with a short chain of amino acids

What class do endorphins belong to?

~ Beta endorphins

Where are peptides found?

~ All throughout the brain and the rest of the brain

~ Are sometimes co-released with classical neurotransmitters