Integration in the nervous system Flashcards
Where do action potentials originate?
Initial segment known as trigger zone, threshold is reduced at trigger zone
What factors determine action potential firing?
Synaptic Input -Temporal / spatial summation - Position of synapses (cell morphology) - Proportion of inhibitory/excitatory synapses - Modulation of synaptic transmission - Facilitation and depression Ion channels properties and expression Electrical properties of cellular membrane
Describe how firing patterns are affected by membrane properties
Membrane resistance (Rm) = V / I V = IRm
Greater resistance produces bigger voltage change
(because less electric charge is leaking out)
Rm ~ 102 ÷ 106 W*cm2
Membrane Capacitance (Cm) Cm ~ 1µF/cm2
Membrane acts like capacitor plates
Time constant tM = Cm x Rm
Greater the time constant → slower membrane potential changes
Types of summation
Spatial summation ( two action potentials as PSP rises above threshold
Temporal summation ( With the third hump AP begins)
Describe how synaptic position will affect properties of synaptic potential
Dendrites passive Signals fade with distance Lambda (l) is the length constant l is the distance a signal decrements 1/e or to ~ 37 %
Attenuation factor (λ) depends on the diameter of the dendrites
Potentials propagate
Passively
Potentials will
decrement
How can frequency of AP firing be translated into amount of neurotransmitter?
Integration in the nerve terminal:
- Action potential activates the Ca2+-channels in the
presynaptic terminal
- The influx of Ca2+ is amplified by release from endoplasmic
reticulum (Ca2+-induced Ca-Release and IP3-mediated release)
- Ca2+ concentration can stay elevated for longer time than
duration of single AP (summation: more APs → more Ca2+)
- Ca2+ concentration affects the number of quanta of
neurotransmitter (multi-vesicular release)
- Ca2+ -level and release probability are influenced by
various presynaptic receptors (usually metabotropic) - Maximal number of neurotransmitter quanta is affected by
depletion and replenishment of synaptic vesicles
Describe modulation of Glutamate release in the
neocortical and hippocampal nerve terminals
Integration at presynaptic site:
Excitatory input is mediated by APs
Major inhibitory input is mediated
by GABAB receptors
Feedback is provided by metabotropic glutamate receptors Feedback can also be provided by ATP (and adenosine), co-released with Glu and released from glial cells as well
How are neurons organized in networks
Principal neurons:
usually excitatory, usually have pyramidal shape,
receive long-range inputs from other circuits
and local inputs from interneurons;
send their axons (innervate) other networks
Interneurons:
usually inhibitory
get most inputs from local principal neurons,
send their outputs locally
What are dendritic spines?
A protrusion from the stalk of a dendrite that synapses with a single axon. Spines have a bulbous head and a thin neck that connects the spine to the stalk of the dendrite. Principal neurons usually have numerous synapses on spines Both principal and interneurons have synapses on dendritic stalk
How are neurons organized in networks?
Activity of network can be expressed as overall rate of APs (Firing rate)
Inhibitory or Excitatory roles for different neurons (receptors) are defined
by their effect on firing rate
• Principal neurons: (usually excitatory) - integrate numerous long-range inputs from other
circuits and local inputs from interneurons and innervate other networks
• Interneurons (usually inhibitory): receive and send signals locally, to modulate
activity of local networks
• In local microcircuits different interneurons can target
different parts of the principle cell
What are the two principal effects of interneurons?
Feed-forward inhibition enhances the effect of the active pathway by suppressing the activity of pathways mediating opposing actions.
is common in monosynaptic
relay and reflex systems
(e.g. in the knee-jerk reflex circuit)
Feed-back inhibition Self-regulating mechanism: Primary (excitatory) neurons of active pathway act on inhibitory interneurons Interneurons, in turn, fire back to primary neurons and thus reduce their probability of firing This action is needed to dampen activity of stimulated pathway and to prevent it over-excitation
What are receptive fields?
The receptive fields of first-order sensory neurons represent
the small area innervated by their terminal branches
(e.g. in the skin, tectorial membrane of cochlea, retina, etc.)
The receptive field of a higher-order (2nd, 3rd…)
neurons is a sum of the receptive fields of
upstream neurons.
Convergence of more first-order neurons
onto second-order neurons translates into
a larger receptive field
Lateral inhibition evoked in second-order relay
neurons by interneurons on the edge of the
receptive field sharpens the second-order sensory
neuron’s receptive field
Describe Glia
Glia can release transmitters:
ATP, glutamate, D-Serine, TNF-a
Glial cells can also communicate to
each other by gap junctions
How is the next level of integration in the NS provided by neuron-glia communication?
• Astrocytes enwrap synaptic terminals
• ~ 90% of brain tissue volume is monitored
by astroglia.
• Individual astrocyte has its own “domain
of responsibility”
• Astrocytes communicate to each other
and to the neighbouring neurons
Signalling in astrocytes - non-excitable cells, so major signal transducer is Ca2+ ( “Ca2+-waves”) - Astrocytes have receptors to number of neurotransmitters: Glutamate, ATP, Ach, GABA, dopamine etc.
Astrocytes “make a bridge “between
neurons and blood vessels
What are the two modes of glia-neuron integration ?
Common key elements:
Astrocytes receive and integrate information
about neuronal activity
Astrocytes communicate to each other
and integrate signals within glial network
Two modes of glia-neuron integration
Neurons Astrocytes Capillary
Mode 1: Astrocytes modulate signalling
in the tripartite synapses and synchronize
activity of local neuronal networks
Mode 2:
Astrocytes mediate neuro-vascular coupling
and regulate metabolic support of neurons
“on demand” (i.e. depending on their activity)