Neurobiology: Introduction

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Neurobiology Introduction

• A brief overview of neuroanatomy and neurobiology

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Neurons

• Neurons are the cells that transmit information
  rapidly in the body.
• Provide mechanism for faster responses to the
  environment

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Three main parts of neurons

• Dendrites
• receive signals
• Cell body
• maintains cell
• Axon
• sends signals

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Dendrites

• Input channel to the neuron
• Most neurons have many dendrites (many inputs)

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• Many dendrites have small spines
• The spines are important as receivers of messages
  from axons.
• Spines are also important in learning and memory.

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Axons

• Output channel from the neuron
• Most neurons have only one axon
• Each axon usually branches many times before it
  ends, allowing a single neuron to have many
  terminals.

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• Because of axon branching, a single neuron may
  send messages to many other neurons (Divergence)
• A single neuron may receive inputs from many
  axons (Convergence)

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• The end of the axon, called the axon terminal, is
  the point at which it communicates with receiving
  neurons.
• Axons usually connect to a receiving neurons
  dendrite, but may also contact a receiving
  neurons cell body or its axon.
• The point where the sending and receiving parts
  of neurons meet is the synapse.

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Synapse

• Neurons communicate with each other at synapses
  using chemical neurotransmitters.

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• Information usually flows across the synapse from
  the axon terminal (presynaptic) to the receiving
  neuron (postsynaptic)

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• Early research showed that electrical stimulation
  would make neurons fire, and would make muscles
  contract.
• However, the rate of electrical transmission in
  neurons was slower than the transmission in metal
  wire.
• Neurons conduct electricity in a special way, by
  a combination of electrical and chemical means.

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Action potential

• The propagation of the electrical impulse in a
  nerve is called the action potential.
• The action potential is initiated at the point
  where the axon emerges from the cell body (the
  axon hillock)
• Once triggered, the action potential travels down
  the axon towards the axon terminal.

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• When the action potential begins in the axon, the
  electrical change in one part of the axon
  membrane triggers a similar change in the
  adjacent parts, and so on, all the way to the
  terminal.
• Normally, action potentials are triggered in a
  cell when the dendrites receive enough input
  signals.
• Action potentials can be triggered artificially
  by electrical stimulation, which makes them easy
  to study.

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• Sherrington showed
• electrical stimulation of sensory nerve produced
  an electrical response in the motor nerve
• electrical stimulation of the motor nerve failed
  to produce an electrical response in sensory
  nerve
• Synapses only transmit in one direction, from
  sensory to motor neurons

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• One-way transmission between neurons occurs
  because synaptic transmission involves the
  release of chemicals (neurotransmitters) from
  storage sites in the presynaptic axon terminal.
• The neurotransmitters are released when action
  potentials propagate down the axon.

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• Release of neurotransmitter by the presynaptic
  cell is a means, not an end.
• Objective is to generate an electrical response
  in the post-synaptic cell.

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• Dendrites are often the receivers of the
  neurotransmitters, but the electrical change
  produced in the dendrite has to be propagated to
  the cell body, and then to the axon, before an
  action potential can occur. This is because the
  action potential is generated at the axon hillock
  where the axon emerges from the cell body.

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• Neurotransmitter arriving from a single
  presynaptic terminal is generally not sufficient
  to produce an action potential in the
  postsynaptic cell.
• Only if the postsynaptic cell receives
  neurotransmitter molecules from many presynaptic
  terminals within a few milliseconds will it cause
  an action potential.

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• Once the postsynaptic cell generates an action
  potential, its role shifts from that of a
  receiver to a sender.
• It now becomes a presynaptic cell that may
• increase likelihood of an action potential in
  postsynaptic cells (excitatory), or
• decrease likelihood of an action potential in
  postsynaptic cells (inhibitory).

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Summary of action potential

• An electrical signal (the action potential)
  causes a chemical event (release of
  neurotransmitter)
• The neurotransmitter crosses the synapse and
  binds to receptor proteins on the postsynaptic
  neuron
• The receptor proteins modulate electrical signals
  in the postsynaptic neuron

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More on neurotransmitters
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Neurotransmitters

• Synthesized in neurons
• Transported to the synapse
• Stored in microscopic sacks called vesicles ready
  for release

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• When the neuron fires, the vesicle merges with
  the cell membrane, releasing the neurotransmitter
  into the synaptic cleft (the gap between two
  neurons).
• The neurotransmitter binds to receptor proteins
  on the postsynaptic neuron (postsynaptic
  receptors) presynaptic neuron (autoreceptors)
• May also bind to receptor proteins on the
  presynaptic neuron (autoreceptors)

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• Receptors recognize only specific
  neurotransmitters (serotonin, dopamine,
  glutamate, etc.)
• Activation of autoreceptors inhibits further
  release of neurotransmitters from the neuron
  (negative feedback).
• May also inhibit synthesis or transport of
  neurotransmitter.

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• Activation of post-synaptic receptors affects ion
  channels on the post-synaptic neuron, which may
  excite or inhibit.
• Some neurotransmitters have no effect on their
  own, but may increase or decrease the effect of
  another neurotransmitter.
• Such neurotransmitters are called
  neuromodulators.
• Hormones and drugs may have these effects.

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• The neurotransmitters may increase or decrease
  the polarization of the neurons cell membrane,
  thus blocking or causing transmission of signal

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Neurotransmitters are inactivated in two ways

• Degraded by enzymes
• Re-absorbed by the presynaptic neuron (reuptake)
• Some anti-depression drugs are Selective
  Serotonin Reuptake Inhibitors (SSRI)
• Some drugs increase or decrease degradation by
  enzymes

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Neural circuits

• Each human brain has billions of neurons that
  collectively make trillions of synaptic
  connections.
• At any one moment, billions of synapses are active

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• A circuit is a group of neurons that are linked
  together by synaptic connections
• A system is a complex circuit that performs a
  specific function, such as seeing or hearing, or
  detecting and responding to danger.

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• For example, seeing involved the detetion of
  light by circuits in the retina, which send
  signals via the optic nerve to the visual part of
  the thalamus, where the information is processed
  by circuits that relay their output to the visual
  cortex, where additional circuits do further
  processing (including retrieving memories of
  related images) and ultimately create visual
  perceptions.

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Projection neurons and interneurons

• Play different roles in circuits and systems
• Projection neurons
• Activate or excite downstream neurons
• Interneurons
• Often inhibit downstream neurons

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Projection neurons

• Have relatively long axons that extend out of the
  area in which their cell bodies are located.
• In a hierarchical circuit, projection neurons
  activate the next projection neurons in the
  circuit
• Do this by releasing neurotransmitter that
  increases the probability that the postsynaptic
  neuron will fire an action potential.

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Interneurons

• Local circuit cells
• Send short axons to nearby neurons, often
  projection neurons
• Often involved in information processing with in
  given level of a hierarchical cicuit.

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Interneurons

• Main function is to regulate flow of synaptic
  traffic by controlling (often limiting) the
  activity of projection neurons.
• Inhibitory interneurons release a
  neurotransmitter from their terminals that
  decreases the likelihood that the postsynaptic
  cell will fire an action potential

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• Projection neurons are usually idle in the
  absence of inputs from other projection neurons.
• Inhibitory neurons are usually active, firing all
  the time (tonic inhibition).
• Part of the reason that projection neurons are
  usually inactive is that they receive inhibitory
  transmitter from interneurons.

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• When excitatory inputs try to turn on a
  projection cell, preexisting inhibition of the
  projection cell has to be overcome.
• The balance between excitatory and inhibitory
  inputs to a neuron determines if it will fire.

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• The amount of inhibition affecting a cell can
  change from moment to moment, depending on other
  factors.
• When projection cells in one area of a circuit
  send enough convergent inputs at about the same
  time to activate projection cells in the next
  area, the level of inhibition in the 2nd area
  usually goes up, because the excitatory inputs
  also activate the interneurons.

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• The momentary increase in excitatory inputs to
  interneurons leads to a momentary increase in
  their inhibitory behavior, which in turn produces
  a momentary inhibition of the projection neurons.
  
• This elicited inhibition is in contrast to
  tonic inhibition.

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Inhibition

• Helps filter out random excitatory inputs so that
  they do not trigger activity
• Protects projection neurons from over-activation,
  which can damage them.

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Glutamate

• Projection neurons require a neurotransmitter
  that has two properties
• Fast acting, to enable fast response to the
  environment
• Ability to excite postsynaptic neurons (increase
  the likelihood of an action potential)
• Glutamate is the main transmitter in projection
  neurons throughout the brain.
• Glutamate is an amino acid

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• Inhibitory neurons release the amino acid GABA
  (gamma-aminobutyric acid)
• GABA reduces the likelihood that an action
  potential will fire in the postsynaptic cell.

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• GABA, glutamate, and other neurotransmitters work
  by attaching to receptor proteins on the
  postsynaptic cell.
• Receptors selectively recognize and bind to
  transmitter molecules.
• Glutamate receptors recognize and bind glutamate,
  but ignore GABA, and vice versa

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• At rest, the chemical composition of the cell is
  more negatively charged than the fluid outside
  the cell.
• The charge difference is caused by the cell
  pumping differently charged ions in and out of
  the cell.

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• The inside of a neuron that is not being excited
  or inhibited is about 60 millivolts (60
  one-thousandths of a volt) more negative than the
  outside.
• The resting potential or the membrane
  potential of the nerve cell at rest is therefore
  -60 millivolts

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• The neuron at rest has a negative charge inside
  (relative to outside)
• When the neuron is stimulated by excitatory
  inputs from other neurons, the inside of the cell
  becomes more positive (the membrane potential
  becomes more positive).

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• The cell interior becomes more positive because
  of the effects of the neurotransmitter glutamate.
• The glutamate receptor spans the cell membrane,
  with part facing inside the cell and part facing
  out.
• When glutamate (glu) released from a presynaptic
  cell binds to the glu receptor, a channel opens
  up through the receptor, allowing positively
  charged ions from the extracellular fluid to
  enter the cell.

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• If enough glu receptors are occupied on the
  postsynaptic cell at about the same time, and the
  voltage inside becomes sufficiently positive,
  then an action potential occurs.

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• In contrast, when GABA receptors are occupied,
  the inside of the cell becomes more negatively
  charged, due to the influx of negative ions,
  especially chloride ions, the a channel in the
  GABA receptor.
• This makes it harder for glutamate released from
  other terminals to change the concentration of
  positive ions in the postsynaptic cell enough to
  trigger an action potential.

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• Whether an action potential occurs depends on the
  balance between excitation (glutamate) and
  inhibition (GABA).
• Because each cell receives many excitatory and
  inhibitory inputs from many other cells, the
  likelihood of firing at any time depends on the
  net balance across all the inputs at that time.

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• Glutamate receptors tend to be located far out on
  the dendrites, especially in the spines.
• GABA receptors tend to be found on the cell body,
  or on the part of the dendrites close to the cell
  body.
• For glutamate-mediated excitation to reach the
  cell body, it has to get past the GABA guard.

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• Without GABA inhibition, neurons could keep
  firing action potentials continuously under the
  influence of glutamate, and eventually will die.
• This has been demonstrated in experiments with
  GABA blockers.
• Glutamate over-excitation is an important cause
  of neuron injury in stroke, epilepsy, and
  possibly other brain disorders.

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• Monosodium glutamate, a meat tenderizer used in
  some food preparation, can increase the amount of
  glutamate in the body, causing headaches, ringing
  ears, and other symptoms.

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• Some drugs work by regulation of GABA
• The anti-anxiety drug Valium works by enhancing
  GABAs ability to counteract glutamate.
• Excitatory inputs that would normally elicit
  anxiety by firing action potentials in fear
  circuits are less able to do so in the presence
  of Valium and related drugs.

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Neuromodulators

• Neuromodulators are neurotransmitters that alter
  (increase or decrease) the effects of other
  neurotransmitters.
• Neuromodulators act more slowly than glutamate
  and GABA, but have longer-lasting effects.

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Three types of neuromodulators

• Peptides
• Amines
• Hormones

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Peptide neuromodulators

• A large class of slow acting modulators found
  throughout the brain
• Made of many amino acids, and are larger than
  single amino acids like glutamate or GABA.
• Peptides are often present in the same axon
  terminals as GABA or glu (but in their own
  vesicles), and are released at the same time when
  an action potential fires.