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PHYSL 372 - Systems Neuroscience > Interneuron Networks > Flashcards

Interneuron Networks Flashcards

1
Q

How to Measure Brain Connectivity:

How do you see neurons?

A

In order to see neurons you need contrast

  • Golgi Stain Method
    • fills cells with silver-chromate
  • Fluorescent dyes (GFPs)
    • GFP for brain labelling
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2
Q

What are the drawbacks to Golgi stain method and Fluorescent dyes?

A

Both techniques require neurons to be traced out manually or with software

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3
Q

What is the difference between Anterograde Tracing neuron connections and Retrograde tracing?

A
  • Anterograde tracing neural connections
    • Carry dyes/fluorescent proteins through axons to be visualized
    • Dyes, viruses (adenoassociated viruses (AAVs))
  • Retrograde tracing
    • Dye or compound gets incorporated into the axon and travels backward to the cell body
    • Cholera toxin, fast blue. Adenoassociated viruses (AAVs), Rabies
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4
Q

What are four techniques to stimulate neurons?

A
  1. Electrical stimulation
  2. Light stimulation (optogenetics)
  3. Chemical stimulation (pharmacogenetics)
  4. Patch clamp single cell stimulation
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5
Q

Electrical Stimulation:

  • Technique
  • Pros/Cons
A

Electrical Stimulation:

  • Technique
    • place wire into brain tissue
    • pass current into tissue to depolarize neurons near the electrode
    • Record from another brain region to see if neurons respond to stimulation
  • Pros/Cons
    • Pros
      • easy to implement
      • effective (repeatable)
      • Precise activation onset
    • Cons
      • Indirect, unintended activation of other neurons close to the stimulation electrode
      • antidromic activation of post-synaptic cells
      • ie no specificity to which region is responding to stimulation
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6
Q

Optogenetic Stimulation

  • Technique
  • Pros
  • Cons
A

Optogenetic Stimulation

  • Technique
    • light sensitive rhodopsin is genetically expressed in neurons of interest
    • In the presence of light, cells are depolarized and can be activated
  • Pros
    • Rapid control of spike timing
    • specific (genetically defined) neuron types can be activated without unintended activation of nearby neurons in the brain
  • Cons
    • Light can change the temperature of neural tissue
    • Must deliver light to the brain using brain implants
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7
Q

What is the first light dependent depolarization opsin used to activate neurons?

A

Channelrhodopsin (ChR2) - responds to blue light

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8
Q

Chemogenetic stimulation

  • Technique
  • Pros
  • Cons
A

Chemogenetic stimulation

  • Technique
    • Designer (bioengineered) receptor is expressed in cells of interest using genetic approaches
    • Receptor is designed to be activated by a specific ligand (drug)
  • Pros
    • cells can be activated by simply applying a drug
    • Drug acts specifically on the designer receptors
    • Specific cell types can be activated
  • Cons
    • No precise control over the timing of activation
      • ie drug action can be long
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9
Q

Paired Patch Clamp Recordings

  • Technique
  • Pros
  • Cons
A

Paired Patch Clamp Recordings

  • Technique
    • 2 single neurons are recorded using intracellular techniques (so that they can be depolarized with current injection)
  • Pros
    • Definitive test of connectivity between neurons in the brain
    • Only true physiological way to test connectivity between neurons
  • Cons
    • Challenging to implement (hard technique)
    • High failure rate
    • Only useful for testing close connections
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10
Q

Cortical Connectivity: micro vs macro

  • Basic Connectivity Rules
    • Within brain region
    • Between brain regions
    • Long range
    • Micro connections
A

Cortical Connectivity: micro vs macro

  • Basic Connectivity Rules
    • Within brain region
      • Cells close to each other are more likely to connect to each other
    • Between brain regions
      • there is no (or weak) relation between distance and connectivity
    • Long-range connections
      • Majority are excitatory
    • Micro connections
      • majority are inhibitory
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11
Q

What are the two neuron types?

A
  • Excitatory - pyramidal cells
  • Inhibitory cells - Interneurons
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12
Q
  • Excitatory - pyramidal cells
    • release ______
    • action
    • Morphology
    • Projection
  • Inhibitory cells - Interneurons
    • release _____
    • action
    • morphology
    • projection
A
  • Excitatory - pyramidal cells
    • release Glutamate
    • action:
      • excite post synaptic cell
    • Morphology
      • larger in diameter
      • many dendritic spines
    • Projection
      • project locally to nearby cells and to different regions of the brain
  • Inhibitory cells - Interneurons
    • release GABA
    • action
      • inhibit post-synaptic cell
    • morphology
      • smaller in diameter
      • generally lacking spines
    • projection
      • mainly project locally within 0.2mm (recieve input from other regions but inhibit locally)
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13
Q

What are the four interneurons and their connections?

A
  • Parvalbumin (PV)
    • Synapse on cell bodies
    • GABA-A mediated inhibition
  • Somatostatin (SST)
    • Synapse on dendrites
    • GABA-A mediated inhibition
  • Vasoactive intestinal polypeptide (VIP)
    • synapse on other interneurons
    • GABA-A mediated inhibition
  • Neuropeptide Y/Neurogliaform cells (NG)
    • express nitric oxide synthase and Neuropeptide Y
    • Synapse on other interneurons AND excitatory cells
    • GABA-B and Volume transmission
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14
Q

Label the types of inhibition represented by colour

A

Blue: Feedforward inhibition

Red/Blue: Feedback inhibition

Red: Lateral inhibition

Green: Disinhibition

Yellow: Volume inhibition

Black: Feedforward excitation

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15
Q

What is feedforward inhibition?

What type of neurons typically mediate feedforward inhibition

Purpose?

Gone wrong?

A
  • Inputs activate interneurons (without necessarily activating pyramidal cells)
  • PV (parvalbumin) cells mediate feedforward inhibition
  • Feedforward inhibition acts to filter inputs
  • With no PV cells, pyramidal cells fire in excess, similar to epilepsy
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16
Q

Feedback inhibition:

  • Definition
  • Type of interneuron
  • Purpose
A

Feedback inhibition:

  • Definition
    • when excitation in one cell activates an interneuron to generate inhibition of itself
  • Type of interneuron
    • PV and SST cells can both participate in feedback inhibition
      • PV=Parvalbumin
      • SST = Somatostatin
  • Purpose
    • Provides stability (prevents excess excitation)
  • FB inhibition arises from local excitation in neural circuits (in contrast with FF inhibition which can be generated by long range excitation)
17
Q

Lateral Inhibition:

  • Definition
  • Interneurons
  • Purpose
A

Lateral Inhibition:

  • Definition
    • one pyramidal cell activates an interneuron to inhibit another pyramidal cell
  • Interneurons
    • SST cells mediate lateral inhibition
    • W/o SST cells, other pyramidal cells can fire when they’re not supposed to
  • Purpose
    • Generates segregation btwn neural groups
    • Allows firing of one cell to stand out
18
Q

Disinhibition

  • Definition
  • Interneurons
A

Disinhibition

  • Definition
    • inhibit inhibitory cell connectivity creating net excitation of another cell population
  • Interneurons
    • VIP→SST connection is disinhibitory with respect to pyramidal cells
    • Without VIP (vasoactive intestinal polypeptide) cells, pyramidal cells fire less
19
Q

Volume inhibition

  • Definition
  • act at
    *
A

Volume inhibition

  • Definition
    • Neurogliaform cells release GABA and act on GABA-B receptors and GABA-A (slow) receptors
  • Effects can be synaptic & extrasynaptic
    • NG cell can therefore influence activity in a non-synaptic way
20
Q

Feedforward excitation

  • Definition
  • Connections
A
  • Definition:
    • Excitatory cells mediate excitation of other neurons
    • An essential feature of communication within and between brain regions
  • Connections between pyramidal cells is 3-10% so connectivity is relatively infrequent
    • however, most neurons are excitatory so a small number of pyramidal cells can exert a lot of excitation
  • Feedforward excitation is usually specific: neurons that “code” for 1 stimulus will communicate
21
Q

Feedforward excitation

  • Definition
  • Connections
A
  • Definition:
    • Excitatory cells mediate excitation of other neurons
    • An essential feature of communication within and between brain regions
  • Connections between pyramidal cells is 3-10% so connectivity is relatively infrequent
    • however, most neurons are excitatory so a small number of pyramidal cells can exert a lot of excitation
  • Feedforward excitation is usually specific: neurons that “code” for 1 stimulus will communicate
22
Q

What is meant by balanced excitation and inhibition?

A
  • The thalamus excites layer 4 of the visual cortex
  • Interneurons are also excited by thalamic input
  • Inhibition strength and excitation strength are correlated
  • Small increases in the excitation:inhibition ration generates APs
23
Q

When you move, you generate “self-generated sounds”. How does the brain tune-out these sounds in order to allow other sounds to be heard while moving

A
  • Feedforward inhibition
  • Motor cortex is activated during movement (eg running)
  • Excitatory neurons from motor cortex activate PV interneurons in auditory cortex
  • PV interneurons suppress auditory cortex during movement
    • Free up space for external stimuli
24
Q
  • Gamma rhythms can be recorded from the _____ during periods of _______
  • They require the activity of ______
  • _______→_______ sequences, usually give rise to _____ activity
  • Decay of inhibitory potentials can control the _______ of firing in ______
A
  • Gamma rhythms can be recorded from the cortex during periods of increased attention
  • They require the activity of both excitatory (pyramidal) cells and interneurons
  • excitation→inhibition sequences, usually give rise to rhythmic activity
  • Decay of inhibitory potentials can control the frequency of firing in pyramidal cells
25
Q
  • What type of inhibition participates in Gamma rhythm generation?
  • What stimuli can evoke gamma rhythms in the visual cortex
  • Suppressing ______ decreases gamma rhythms
    *
A
  • What type of inhibition participates in Gamma rhythm generation?
    • feedback and feedforward inhibition
  • What stimuli can evoke gamma rhythms in the visual cortex
    • visual stimuli
  • Suppressing SST cells decreases gamma rhythms
    • suggests feedback inhibition plays a role
  • Feedforward inhibition also plays a role in generating gamma rhythms in other neural structures like the hippocampus
26
Q

Surround suppression (lateral inhibition) in the visual cortex:

  • Pyramidal cells in V1 ______ their firing with larger stimuli than outside their receptive field (surround suppression)
  • _____ interneuron increases their activity
  • Surround suppression arises from _______
  • May participate in ability to _______
A
  • Pyramidal cells in V1 decrease their firing with larger stimuli than outside their receptive field (surround suppression)
  • SST interneuron increases their activity
  • Surround suppression arises from lateral inhibition
  • May participate in perceptual ability to recognize continuity of objects in the visual field
27
Q

Disinhibition (brain state - locomotion)

  • During locomotion, ____ become active even with no visual stimuli
  • ____ cells are activated by acetylcholine which induces _____
A

Disinhibition (brain state - locomotion)

  • During locomotion, V1 cells become active even with no visual stimuli
  • VIP cells are activated by acetylcholine which induces disinhibition of pyramidal cells

VIP = vasoactive intestinal polypeptide (VIP) interneurons

28
Q

What is the role if VIP and SST in control of blood flow?

A
  • VIP induces vasodilation, increasing blood flow (increase excitation to increase blood flow to active regions)
  • SST induces vasoconstriction, decreasing blood flow
  • Similar opposing actions at the level of blood flow and regulating excitability in pyramidal cells

VIP increases → SST decreases → excitation increases

29
Q

What is global inhibition? What gene is associated and which interneurons show that gene

A

Sleep

  • c-fos is an immediate-early gene that indicates neurons with high AP firing rates
  • Following sleep, NG cells show c-fox in the cortex
  • Other cell types do not show c-fox
  • NG cells may cause decreased cortical activity during sleep
30
Q

What four processes all require unique contributions from different types of neurons as discussed in class?

A

Gamma rhythms

Locomotion

Auditory processing

Visual coding

PHYSL 372 - Systems Neuroscience (16 decks)

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