Neuroscience Final Exam
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Neuroscience Final Exam Notes
Molecular Signaling Within Neurons:
Electrical and chemical signaling mechanisms allow one nerve cell to receive and transmit information to
another
Intracellular processing/signaling typically begins when extracellular chemical signals (e.g. neurotransmitters,
hormones, trophic factors) bind to specific receptors located either on the surface or within the cytoplasm or
nucleus of the target cells
o Binding activates the receptors and stimulates cascades of intracellular reactions involving GRP-binding
proteins, second messenger molecules, protein kinases, ion channels, and other effector proteins whose
modulation temporarily changes the physiological state of the target cell
The intracellular signal transduction pathways can also cause longer lasting changes by altering the transcription
of genes thus affecting the protein composition of the target cells on a more permanent basis
Large number of components involved in intracellular signaling pathways allows precise temporal and spatial
control over the function of individual neurons thus allowing the coordination of electrical and chemical activity
in the related populations of neurons that comprise neural circuits and systems
Strategies of Molecular Signaling:
Neurons receive signals from other neurons (via neurotransmitters) and other cells (via hormones, growth
factors, trophic factors)
o Neurons have specialized machinery that can transduce these signals to changes in their physiological
state
Neurons can change their state (ie which receptors, channels, neurotransmitters, etc they open, close, modulate
or express) depending on what they perceive is going on in their environments
Synaptic transmission is a special form of chemical signaling that transfers information from one neuron to
another
o Chemical signaling is not limited to synapses
Paracrine signaling acts over a longer range than synaptic transmission and involves the secretion of chemical
signals onto a group of nearby target cells
o Chemical signaling that acts over a short range (but longer than synaptic signaling)
o A secretory cell secretes chemicals that target receptors on adjacent target cells
Endocrine signaling is the secretion of hormones into the bloodstream where they can affect targets throughout
the body
o Endocrine cells secrete hormones into the blood which travels and binds to receptors of distant target
cells
Membrane protein signaling- two cells next to each other signal through membrane proteins
o Membrane-attached proteins bind to receptors on adjacent target cells
Autocrine signaling is the way in which a cell talks/signals itself
o Cell secretes chemicals that bind to receptors on the same cell
Figure 7.1: chemical signaling
o The essential components of chemical signaling are cells that initiate the process by releasing signaling
molecules, specific receptors on target cells, second messenger target molecules, and subsequent
cellular responses
o Forms of chemical communication include synaptic transmission, paracrine signaling, and endocrine
signaling
Chemical signaling of any sort requires three components: a signal, a receptor, and a target
o A molecular signal transmits information from one cell to another
o A receptor molecule transduces the information provided by the signal
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o A target molecule mediates the cellular response
o Intracellular signal transduction is the part of the process that takes place within the confines of the
target cell
E.g. of transduction in intercellular communication is the sequence of events triggered by chemical synaptic
transmission
o Neurotransmitters serve as the signal, neurotransmitter receptors serve as the transducing receptor, the
target molecule is an ion channel that is altered to cause the electrical response of the postsynaptic cell
o In many cases synaptic transmission activates additional intracellular pathways that have a variety of
functional consequences
E.g. binding of the neurotransmitter norepinephrine to its receptor activates GTP-binding
proteins that produce second messengers within the postsynaptic target, activate enzyme
cascades, and eventually change the chemical properties of numerous target molecules within
the affected cell
Signal amplification is a general advantage of chemical signaling in both intercellular and intracellular contexts
o Occurs because individual signaling reactions can generate a much larger number of molecular products
than the number of molecules that initiate the reaction
o A small number of signal molecules can ultimately activate a very large number of target molecules
(because the transduction processes are often mediated by a sequential set of enzymatic reactions each
with its own amplification factor)
o Amplification guarantees that a physiological response is evoked in the face of other, potentially
countervailing, influences
Figure 7.2: Amplification in signal transduction pathways
o The activation of a single receptor by a signaling molecule (e.g. the neurotransmitter norepinephrine)
can lead to the activation of numerous G-proteins inside cells
o These activated proteins can bind to other signaling molecules (e.g. the enzyme adenylyl cyclase)
o Each activated enzyme molecule generates a large number of cAMP molecules
o cAMP binds to and activates another family of enzymes (protein kinases) that can phosphorylate many
target proteins
o Overall the cascade results in a tremendous increase in the potency of the initial signal
Signal transduction schemes permit precise control of cell behavior over a wide range of times
o Some molecular interactions allow information to be transferred rapidly while others are slower and
longer lasting
o To encode information that varies over time, the concentration of the relevant signaling molecules must
be carefully controlled
The concentration of every signaling molecule within the signaling cascade must return to
subthreshold value before the arrival of another stimulus
Keeping the intermediates in a signaling pathway activated is critical for a sustained response
Having multiple levels of molecular interactions facilitates the intricate timing of these events
Activation of Signaling Pathways:
Molecular components of signal transduction pathways are always activated by a chemical signaling molecules
There are three classes of signaling molecules: cell-impermeant, cell-permeant, and cell-associated
o Cell- impermeant and permeant are secreted molecules thus can act on target cells removed from the
site of signal synthesis or release
Cell-impermeant signaling molecules typically bind to receptors associated with cell membranes
o E.g. some neurotransmitters, proteins such as neurotrophic factors, and peptide hormones such as
glucagon, insulin, and various reproductive hormones
o These signaling molecules are typically short-lived because they are rapidly metabolized or because they
are internalized by endocytosis once bound to their receptors
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Cell-permeant signaling molecules can cross the plasma membrane to act directly on receptors that are inside
the cell
o E.g. numerous steroid (glucocorticoids, estradiol, and testosterone) and thyroid hormones, and retinoids
o These signaling molecules are relatively insoluble in aq solutions and are often transported in blood and
other extracellular fluids by binding to specific carrier proteins
In this form they many persist in the bloodstream for hours or even days
Cell-associated signaling molecules are arrayed on the extracellular surface of the plasma membrane
o These molecules only act on other cells that are physically in contact with the cell that carries such
signals
o E.g. proteins such as integrins and neural cell adhesion molecules (NCAMs) that influence axonal growth
o Membrane-bound signaling molecules are more difficult to study but are important in neuronal
development and other circumstances where physical contact between cells provides information about
cellular identities
Figure 7.3: Three classes of cell signaling molecules
o Cell-impermeant molecules cannot readily traverse the plasma membrane of the target cell and must
bind to the extracellular portion of transmembrane receptor proteins
o Cell-permeant molecules are able to cross the plasma membrane and bind to receptors in the cytoplasm
or nucleus of target cells
o Cell-associated molecules are presented on the extracellular surface of the plasma membrane
These signals activate receptors on target cells only if they are directly adjacent to the signaling
cell
Receptor Types:
Cellular responses are determined by the presence of receptors that specifically bind the signaling molecules
Binding of signal molecules causes a conformational change in the receptor that then triggers the subsequent
signaling cascade within the affected cell
The receptors for impermeant signal molecules are membrane-spanning proteins
o The extracellular domain of such receptors includes the binding site for the signal while the intracellular
domain activates intracellular signaling cascades after the signal binds
o Channel-linked/ligand-gated ion channels, enzyme-linked receptors, and G-protein linked receptors
Channel-linked receptors (ligand-gated ion channels) have the receptor and transducing functions as part of the
same protein molecule
o Interaction of the chemical signal with the binding site of the receptor causes the opening or closing of
an ion channel pore in another part of the same molecules
The resulting ion flux changes the membrane potential of the target cell and can also lead to
entry of Ca2+ ions (serve as a second messenger signal within the cell) in some cases
o E.g. ionotropic neurotransmitter receptors
E.g. the ACh receptor at the endplate. Neurotransmitter is the signal
Enzyme-linked receptors have an extracellular binding site for chemical signals
o The intracellular domain of such receptors is an enzyme whose catalytic activity is regulated by the
binding of an extracellular signal
o The majority of these receptors are protein kinases (often tyrosine kinases) that phosphorylate
intracellular target proteins thereby changing the physiological function of the target cells
o E.g. Trk family of neurotrophin receptors and other receptors for growth factors
o Signal through protein kinases or protein phosphatases. Protein modification then alters intracellular
enzyme activity
G-protein-coupled receptors regulate intracellular reactions by an indirect mechanism involving an intermediate
transducing molecule (GTP-binding porteins/G-proteins)
o Signal through G-proteins. The proteins can alter the function of many proteins
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Notes_COMPLETE
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Neuroscience Final Exam Notes
Molecular Signaling Within Neurons:
Electrical and chemical signaling mechanisms allow one nerve cell to receive and transmit information to
another
Intracellular processing/signaling typically begins when extracellular chemical signals (e.g. neurotransmitters,
hormones, trophic factors) bind to specific receptors located either on the surface or within the cytoplasm or
nucleus of the target cells
o Binding activates the receptors and stimulates cascades of intracellular reactions involving GRP-binding
proteins, second messenger molecules, protein kinases, ion channels, and other effector proteins whose
modulation temporarily changes the physiological state of the target cell
The intracellular signal transduction pathways can also cause longer lasting changes by altering the transcription
of genes thus affecting the protein composition of the target cells on a more permanent basis
Large number of components involved in intracellular signaling pathways allows precise temporal and spatial
control over the function of individual neurons thus allowing the coordination of electrical and chemical activity
in the related populations of neurons that comprise neural circuits and systems
Strategies of Molecular Signaling:
Neurons receive signals from other neurons (via neurotransmitters) and other cells (via hormones, growth
factors, trophic factors)
o Neurons have specialized machinery that can transduce these signals to changes in their physiological
state
Neurons can change their state (ie which receptors, channels, neurotransmitters, etc they open, close, modulate
or express) depending on what they perceive is going on in their environments
Synaptic transmission is a special form of chemical signaling that transfers information from one neuron to
another
o Chemical signaling is not limited to synapses
Paracrine signaling acts over a longer range than synaptic transmission and involves the secretion of chemical
signals onto a group of nearby target cells
o Chemical signaling that acts over a short range (but longer than synaptic signaling)
o A secretory cell secretes chemicals that target receptors on adjacent target cells
Endocrine signaling is the secretion of hormones into the bloodstream where they can affect targets throughout
the body
o Endocrine cells secrete hormones into the blood which travels and binds to receptors of distant target
cells
Membrane protein signaling- two cells next to each other signal through membrane proteins
o Membrane-attached proteins bind to receptors on adjacent target cells
Autocrine signaling is the way in which a cell talks/signals itself
o Cell secretes chemicals that bind to receptors on the same cell
Figure 7.1: chemical signaling
o The essential components of chemical signaling are cells that initiate the process by releasing signaling
molecules, specific receptors on target cells, second messenger target molecules, and subsequent
cellular responses
o Forms of chemical communication include synaptic transmission, paracrine signaling, and endocrine
signaling
Chemical signaling of any sort requires three components: a signal, a receptor, and a target
o A molecular signal transmits information from one cell to another
o A receptor molecule transduces the information provided by the signal
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o A target molecule mediates the cellular response
o Intracellular signal transduction is the part of the process that takes place within the confines of the
target cell
E.g. of transduction in intercellular communication is the sequence of events triggered by chemical synaptic
transmission
o Neurotransmitters serve as the signal, neurotransmitter receptors serve as the transducing receptor, the
target molecule is an ion channel that is altered to cause the electrical response of the postsynaptic cell
o In many cases synaptic transmission activates additional intracellular pathways that have a variety of
functional consequences
E.g. binding of the neurotransmitter norepinephrine to its receptor activates GTP-binding
proteins that produce second messengers within the postsynaptic target, activate enzyme
cascades, and eventually change the chemical properties of numerous target molecules within
the affected cell
Signal amplification is a general advantage of chemical signaling in both intercellular and intracellular contexts
o Occurs because individual signaling reactions can generate a much larger number of molecular products
than the number of molecules that initiate the reaction
o A small number of signal molecules can ultimately activate a very large number of target molecules
(because the transduction processes are often mediated by a sequential set of enzymatic reactions each
with its own amplification factor)
o Amplification guarantees that a physiological response is evoked in the face of other, potentially
countervailing, influences
Figure 7.2: Amplification in signal transduction pathways
o The activation of a single receptor by a signaling molecule (e.g. the neurotransmitter norepinephrine)
can lead to the activation of numerous G-proteins inside cells
o These activated proteins can bind to other signaling molecules (e.g. the enzyme adenylyl cyclase)
o Each activated enzyme molecule generates a large number of cAMP molecules
o cAMP binds to and activates another family of enzymes (protein kinases) that can phosphorylate many
target proteins
o Overall the cascade results in a tremendous increase in the potency of the initial signal
Signal transduction schemes permit precise control of cell behavior over a wide range of times
o Some molecular interactions allow information to be transferred rapidly while others are slower and
longer lasting
o To encode information that varies over time, the concentration of the relevant signaling molecules must
be carefully controlled
The concentration of every signaling molecule within the signaling cascade must return to
subthreshold value before the arrival of another stimulus
Keeping the intermediates in a signaling pathway activated is critical for a sustained response
Having multiple levels of molecular interactions facilitates the intricate timing of these events
Activation of Signaling Pathways:
Molecular components of signal transduction pathways are always activated by a chemical signaling molecules
There are three classes of signaling molecules: cell-impermeant, cell-permeant, and cell-associated
o Cell- impermeant and permeant are secreted molecules thus can act on target cells removed from the
site of signal synthesis or release
Cell-impermeant signaling molecules typically bind to receptors associated with cell membranes
o E.g. some neurotransmitters, proteins such as neurotrophic factors, and peptide hormones such as
glucagon, insulin, and various reproductive hormones
o These signaling molecules are typically short-lived because they are rapidly metabolized or because they
are internalized by endocytosis once bound to their receptors
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Cell-permeant signaling molecules can cross the plasma membrane to act directly on receptors that are inside
the cell
o E.g. numerous steroid (glucocorticoids, estradiol, and testosterone) and thyroid hormones, and retinoids
o These signaling molecules are relatively insoluble in aq solutions and are often transported in blood and
other extracellular fluids by binding to specific carrier proteins
In this form they many persist in the bloodstream for hours or even days
Cell-associated signaling molecules are arrayed on the extracellular surface of the plasma membrane
o These molecules only act on other cells that are physically in contact with the cell that carries such
signals
o E.g. proteins such as integrins and neural cell adhesion molecules (NCAMs) that influence axonal growth
o Membrane-bound signaling molecules are more difficult to study but are important in neuronal
development and other circumstances where physical contact between cells provides information about
cellular identities
Figure 7.3: Three classes of cell signaling molecules
o Cell-impermeant molecules cannot readily traverse the plasma membrane of the target cell and must
bind to the extracellular portion of transmembrane receptor proteins
o Cell-permeant molecules are able to cross the plasma membrane and bind to receptors in the cytoplasm
or nucleus of target cells
o Cell-associated molecules are presented on the extracellular surface of the plasma membrane
These signals activate receptors on target cells only if they are directly adjacent to the signaling
cell
Receptor Types:
Cellular responses are determined by the presence of receptors that specifically bind the signaling molecules
Binding of signal molecules causes a conformational change in the receptor that then triggers the subsequent
signaling cascade within the affected cell
The receptors for impermeant signal molecules are membrane-spanning proteins
o The extracellular domain of such receptors includes the binding site for the signal while the intracellular
domain activates intracellular signaling cascades after the signal binds
o Channel-linked/ligand-gated ion channels, enzyme-linked receptors, and G-protein linked receptors
Channel-linked receptors (ligand-gated ion channels) have the receptor and transducing functions as part of the
same protein molecule
o Interaction of the chemical signal with the binding site of the receptor causes the opening or closing of
an ion channel pore in another part of the same molecules
The resulting ion flux changes the membrane potential of the target cell and can also lead to
entry of Ca2+ ions (serve as a second messenger signal within the cell) in some cases
o E.g. ionotropic neurotransmitter receptors
E.g. the ACh receptor at the endplate. Neurotransmitter is the signal
Enzyme-linked receptors have an extracellular binding site for chemical signals
o The intracellular domain of such receptors is an enzyme whose catalytic activity is regulated by the
binding of an extracellular signal
o The majority of these receptors are protein kinases (often tyrosine kinases) that phosphorylate
intracellular target proteins thereby changing the physiological function of the target cells
o E.g. Trk family of neurotrophin receptors and other receptors for growth factors
o Signal through protein kinases or protein phosphatases. Protein modification then alters intracellular
enzyme activity
G-protein-coupled receptors regulate intracellular reactions by an indirect mechanism involving an intermediate
transducing molecule (GTP-binding porteins/G-proteins)
o Signal through G-proteins. The proteins can alter the function of many proteins
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