Interneuron Network Connnectivity Flashcards
What are 2 methods of visualizing neurons?
- golgi stain method
- fluorescent dyes
Describe how the golgi stain method allows us to visualize neurons.
- fill cells with silver-chromate
- cells appear black
Describe how fluorescent dyes are used to visualize neurons.
- fluorescent dyes used to LABEL cells using GENETIC APPROACHES
What is the drawback of using golgi staining and fluorescent dyes to visualize neurons?
neurons have to be traced out either manually or with software
anterograde vs retrograde tracing neural connections. what kind of tracers are used?
anterograde:
- carry dyes through axons to be visualized
- tracers: dyes, viruses (AAVs)
retrograde:
- dye travels from AXON BACKWARD TO CELL BODY
- tracers: cholera toxin, fast blue, AAVs, rabies
What are 4 neuron stimulation techniques?
- electrical stimulation
- chemical stimulation
- light stimulation
- patch clamp single cell stimulation
How do neuron stimulation techniques allow us to visualize neural connectivity?
- stimulate neurons
- these neurons stimulate “the other neurons”
- record activities in “the other neurons” (that are part of the network)
Which neuron stimulation technique is the oldest?
electrical stimulation
Describe how to set up electrical stimulation technique.
- place wire into brain tissue and inject current to depolarize neurons near electrode
- record form other brain region to see if neurons respond to stimulation
pros of electrical stimulation
- easy to implement
- effective
- precise activation onset
cons of electrical stimulation
- indirect, UNINTENDED activation of other neurons close to stimulation electrode
- antidromic activation of post-synaptic cells
Describe how to set up optogenetic stimulation.
- light-sensitive RHODOPSIN is genetically expressed in neurons of interest
- light causes cell depolarization and activation
pros of optogenetic stimulation
- rapid control of spike timing
- specific neuron types can be activated WITHOUT UNINTENDED activation of nearby neurons
cons of optogenetic stimulation
- light can change the temperature of neural tissue
- must deliver light to the brain using BRAIN IMPLANTS
Describe how to set up chemogenetic stimulation.
- designer receptor is expressed in cells of interest using genetic approaches
- receptor is ACTIVATED by a SPECIFIC ligand/drug
pros of chemogenetic stimulation
- cells can be activated simply by applying a drug
- drug acts SEPCIFICALLY on designer receptors
- specific cell types can be activated
cons of chemogenetic stimulation
no precise control over timing of activation
Describe the setup of paired patch clamp recording
2 single neurons are recorded using INTRACELLULAR techniques (so that they can be depolarized with current injection)
pros of paired patch clamp recording
definitive test of connectivity between neurons in the brain
(i.e. ONLY TRUE WAY TO TEST CONNECTIVITY BETWEEN NEURONS)
cons of paired patch clamp recording
- challenging to implement (hard technique)
- high failure rate
- only useful for testing close connections
TRUE or FALSE: patch clamp recording can be used to test long connections between neurons
FALSE: only useful for testing CLOSE connections
Which neuron stimulation technique is the only true way to test connectivity between neurons?
paired patch clamp recordings
What is the basic connectivity rule within a brain region?
cells close to each other are more likely to connect to each other
What is the basic connectivity rule between brain regions?
no/weak relation between distance and connectivity
TRUE or FALSE: macro connections are mainly inhibitory and micro connections are mainly excitatory
FALSE:
- micro connection = inhibitory
- macro connection = excitatory
For excitatory cells:
- pyramidal cell or interneuron?
- NT released?
- what percentage of cells in the cortex?
- larger or smaller in diameter?
- project locally or to different brain regions?
- many or lacking in dendritic spines?
- apical or aspiny?
- pyramidal cell
- glutamate
- 90% of cells
- larger in diameter
- project both locally AND to different brain regions
- many dendritic spines
- apical
For inhibitory cells:
- pyramidal cell or interneuron?
- NT released?
- what percentage of cells in the cortex?
- larger or smaller in diameter?
- project locally or to different brain regions?
- many or lacking in dendritic spines?
- apical or aspiny?
- interneuron
- GABA
- 10% of cells
- smaller diameter
- project locally
- lacking in dendritic spines
- aspiny
What are the 4 types of interneurons and their connections?
- IN with parvalbumin (PV)
- IN with somatostatin (SST)
- IN with vasoactive intestinal polypeptide (VIP)
- IN with neuropeptide Y/neurogliaform cells (NG)
What kind of peptide is parvalbumin?
calcium-binding
Which interneuron is the main inhibitory cell?
parvalbumin (PV)
For parvalbumin INs:
- synapse on?
- which layers of the cortex?
- inhibition mediated by which NT?
DRAW
- synapse on cell bodies
- layer 2-6
- GABA inhibition
For somatostatin INs:
- synapse on?
- which layers of the cortex?
- inhibition mediated by which NT?
DRAW
- synapse on dendrites
- layer 2-6
- GABA inhibition
For vasoactive intestinal peptide INs:
- synapse on?
- which layers of the cortex?
- inhibition mediated by which NT?
DRAW
- synapse on OTHER INs
- layer 1-3
- GABA inhibition
For neuropeptide/neurogliaform INs:
- synapse on?
- which layers of the cortex?
- inhibition mediated by which NT?
DRAW
- synapse on OTHER INs AND EXCITATORY CELLS
- layer 1-3
- GABA and volume transmission
Which type of IN is involved in disinhibition?
VIP
Which type of IN inhibits all neuron types?
NG
what is feedforward inhibition?
inputs activate INs (without necessary activation pyramidal cells)
i.e. only activate INs
Which type of IN mediates feedforward inhibition?
PV
What happens to pyramidal cell activity without PV cells?
no feedforward inhibition –> pyramidal cells fire like epilepsy
What is feedback inhibition?
when excitation in one cell activates an IN to generate INHIBITION OF ITSELD
which type of IN mediate feedback inhibtion?
PV and SST
What type of inhibition provides stability?
feedback
TRUE or FALSE: FEEDFORWARD inhibition arises from local excitation, whereas FEEDBACK inhibition can be generated by long-range excitation
FALSE:
- feedback inhibition = micro
- feedforward inhibition = macro
What is lateral inhibition?
one pyramidal cell activates an IN to INHIBIT ANOTHER PYRAMIDAL CELL
Which type of IN mediates lateral inhibition?
SST
What type of inhibition generates segregation between neural groups?
lateral inhibition
Without SST cells in lateral inhibition, what can happen?
OTHER pyramidal cells can fire when they are not supposed to
What is disinhibition?
inhibitory cell –> inhibitory cell connectivity, creating net EXCITATION of ANOTHER CELL POPULATION
Which 2 IN types mediate disinhibition?
VIP–> SST disinhibitory on pyramidal cells
What happens to pyramidal cell activity if VIP cells are not present?
pyramidal cells fire LESS
What is volume inhibition?
neurogliaform cells release GABA, and act on GABA-B and GABA-A receptors
TRUE or FALSE: GABA-A is a slow receptor
TRUE
Which IN type mediates volume inhibition?
NG
TRUE or FALSE: disinhibition effects can be synaptic and extra-synaptic
FALSE: volume inhibition
TRUE or FALSE: SST cells can influence activity in a non-synaptic way
FALSE: NG cells
(because volume inhibition has extra-synaptic effects)
What is feedforward excitation?
excitatory cells mediate excitation of other cells
which type of cortical circuit motif is an essential feature of communication within and between brain regions?
feedforward excitation
What is the percentage of connections between pyramidal cells? Is this frequent or infrequent? Does this mean a large or small number of pyramidal cells are needed to exert a lot of excitation?
3-10%, infrequent, small number needed
TRUE or FALSE: feedforward excitation is usually specific and not general
TRUE
which layer of the visual cortex does the thalamus excite?
layer 4
TRUE or FALSE: inhibition strength and excitation strength are NOT correlated
FALSE: they are correlated
Describe how excitation and inhibition are balanced.
small increases in the excitation:inhibition ration generate APs
Which type of inhibition mediates the “tuning-out” of self-generated sounds? Describe how it works (consider the type of IN involved)?
feedforward inhibition
- motor cortex is activated during movement
- excitatory neurons from motor cortex activate PV interneurons in auditory cortex
- KEY: PV INs suppress auditory cortex during movement
TRUE or FALSE: gamma rhythms only require activity of pyramidal cells
FALSE: both pyramidal cells and INs
When can gamma rhythms be recorded from the cortex?
during periods of increased attention
What can control the frequency of firing of pyramidal cells?
decay of inhibitory potentials
Which type of of inhibition can participate in gamma rhythm generation?
feedforward and feedback inhibition
TRUE or FALSE: auditory stimuli evoke gamma rhythms in the auditory cortex
FALSE: VISUAL stimuli evoke gamma rhythms in the VISUAL cortex
How does suppressing SST affect gamma rhythms? What does this imply?
- decrease gamma rhythms in visual cortex
- implication: feedback inhibition plays a role in regulating gamma rhythms
what type of inhibition plays a role in generating gamma rhythms in the hippocampus?
feedforward inhibition (PV)
Do pyramidal cells in V1 increase or decrease their firing with larger stimuli that are outside of their receptive field? What is the name for this phenomenon?
DECREASE FIRING; surround suppression
Which type of IN’s activity is increased in surround suppression?
SST
what kind of inhibition modulates surround suppression?
lateral inhibition
What kind of inhibition may participate in perceptual ability to recognize CONTINUITY of objects in the visual field?
lateral inhibition
TRUE or FALSE: in surround suppression, SST INs increase their activity, and pyramidal cells decrease their activity, as the size of the object becomes larger
TRUE
TRUE or FALSE: during locomotion, V1 cells are only activated with visual stimuli
FALSE: V1 cells activated even with no visual stimuli
How are V1 cells activated during locomotion even without visual stimuli? Which type of inhibition mediates this? Which INs are involved?
- disinhibition of V1
- VIP cells are activated during locomotion by ACh –> induce disinhibition of pyramidal cells
note: SST is also involved (VIP –> SST)
Does VIP induce vasodilation or vasoconstriction? SST?
- VIP = vasodilation
- SST = vasoconstriction
What is stimulus encoding, which type of circuit connectivity is involved?
- neurons that “code” for 1 stimulus will synapse on each other
- feedforward excitation
When does the cortex exhibit global inhibition?
during sleep
What does the immediate early gene c-fos indicate?
high AP firing rates
How do we know that NG cells may cause decreased cortical activity during sleep?
AFTER SLEEP, neurogliaform cells show c-fos
(sleep-deprived, not much c-fos activation)
Which IN shows c-fos?
NG
TRUE or FALSE: Gabazine acts on GABA-B receptors and it is fast acting
FALSE: it acts on GABA-A, but yes it is fast-acting
