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
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
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
4
Q
What are four techniques to stimulate neurons?
A
- Electrical stimulation
- Light stimulation (optogenetics)
- Chemical stimulation (pharmacogenetics)
- Patch clamp single cell stimulation
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
- Pros
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
7
Q
What is the first light dependent depolarization opsin used to activate neurons?
A
Channelrhodopsin (ChR2) - responds to blue light
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
- No precise control over the timing of activation
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
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
- Within brain region
11
Q
What are the two neuron types?
A
- Excitatory - pyramidal cells
- Inhibitory cells - Interneurons
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)
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
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
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
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
- PV and SST cells can both participate in feedback inhibition
- 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
