Lecture 9 - The Wiring of the Cortex Flashcards
how does the Golgi stain work?
fills cells with silver chromate, making them appear black (creates contrast)
in 1906, Santiago Ramon y Cajal won the Nobel Prize for determining:
how brain cells communicate (unidirectional flow)
fluorescent dyes can be used to:
label cells using genetic approaches
what is the most common fluorescent protein for brain labelling?
green fluorescent protein (GFP)
what is the drawback to using Golgi stains and fluorescent dyes?
neurons have to be traced out either manually or with software
what are anterograde tracing neural connections?
carry dyes/fluorescent proteins through axons, to be visualized
how are anterograde tracing neural connections visualized?
using dyes and viruses (adenoassociated viruses (AAVs))
what are retrograde tracing connections?
dye or compound gets incorporated into the axon and travels backward to the cell body
how are retrograde tracing connections visualized?
using cholera toxin, fast blue, adenoassociated viruses (AAVs), and rabies
what are the four main types of neuron stimulation techniques?
- electrical stimulation
- light stimulation (optogenics)
- chemical stimulations (pharmacogenetics)
- patch clamp single cell stimulation
what is the earliest neurons stimulation technique?
electrical stimulation
neuronal stimulation technique where wires are inserted into brain tissue and current is passed into the tissue to depolarize neurons near the electrode, then record from other brain regions to see if neurons respond to stimulation
electrical stimulation
what are the pros of electrical stimulation?
1) easy to implement (stick a wire into the brain)
2) effective (repeatable across days)
3) precise activation onset
what are the cons of electrical stimulation?
1) indirect, unintended activation of other neurons close to the stimulation electrode
2) antidromic activation of post-synaptic cells
occurs when an impulse travels opposite to the normal direction to that in a normal nerve fiber
antidromic activation of post-synaptic cells
neuronal stimulation technique where a light sensitive rhodopsin is genetically expressed in neurons of interest. in the prescence of certain wavelengths of light, cells are depolarized and can be activated
optogenic stimulation
the first light dependent depolarization opsin used to activate neurons
channelrhodopsin (ChR2)
what are the pros of optogenic stimulation?
1) rapid control of spike timing
2) specific (genetically defined) neuron types can be activated without unintended activation of nearby neurons in the brain
what are the cons of optogenic stimulation?
1) light can change the temperature of neural tissue (have to be very careful when applying light pulses)
2) must deliver light to the brain, using brain implants (very invasive)
neuronal stimulation technique where a bioengineered receptor is expressed in cells of interest using genetic approaches. the receptor is designed to be activated by a specific, exogenous ligand
chemogenetic stimulation
when using chemogenetic stimulation, the cells will depolarize when:
exposed to their specific ligand
what are the pros of using chemogenetic stimulation?
1) cells can be activately by simply applying a drug
2) the drug acts specifically on the designer receptors
3) specific cell types can be activated
what are the cons of using chemogenetic stimulation?
1) no precise control over the timing of activation (cell just does its thing)
within a brain region, cells close to each other are more likely to:
connect to each other
between brain regions, there is little to no relation between:
distance and connectivity
long range connections in the brain are:
mostly excitatory
micro connections are mainly:
inhibition
true or false: local connectivity in the brain is very strong
true
- release glutamate
- excite post-synaptic cells
- 90% of neurons in the cortex
- larger in diameter (8-15 um)
- project locally to nearby cells and to different regions of the brain
- have many dendritic spines
these are all characteristics of:
excitatory cells
excitatory cells are also known as:
pyramidal cells
- release GABA
- inhibits the post-synaptic cells
- 10% of neurons in the cortex
- smaller in diameter
- mainly project locally (within 0.2mm)
- generally lacking spines
these are all characteristics of:
inhibitory cells
inhibitory cells are also known as:
interneurons
what are the four main types of interneurons in the cortex?
- parvalbumin (PV)
- somatostatin (SST)
- vasoactive intestinal polypeptide (VIP)
- neuropeptide Y/neurogliaform cells (NG)
type of interneuron that synapses onto cell bodies, is found in cortical layers 2-6, and work by GABA-A mediated inhibition
parvalbumin (PV) interneurons
what is parvalbumin?
a calcium binding protein
type of interneuron that synapses onto dendrites, is found in cortical layers 2-6, and works by GABA-A mediated inhibition
somatostatin (SST) interneurons
somatostatin interneurons allow for:
fine tuning and control of dendrites
type of interneuron that synapses onto other interneurons, is found mainly in cortical layers 1-3, and works by GABA-A mediated inhibition
vasoactive intestinal polypeptide (VIP) interneurons
vasoactive intestinal polypeptide (VIP) interneurons allow for:
cells to pass signals to other cells and cortical layers
type of interneuron that synapses onto other interneurons and excitatory cells, is found in cortical layers 1-3, and works by GABA-B and volume transmission
neuropeptide Y/neurogliaform (NG) interneurons
what compounds do neurogliaform cells express?
nitric oxide synthase and neuropeptide Y
what is feedforward inhibition?
inputs activate interneurons which inhibit the activity of pyramidal cells
what types of cells mediate feedforward inhibition?
parvalbumin (PV) cells
what is the purpose of feedforward inhibition?
acts to filter inhibition
with no PV cells, pyramidal cells fire:
in excess (similar to epilepsy)
what is feedback inhibition?
when excitation in one cell activates an interneuron to generate inhibition of itself
what types of cells mediate feedback inhibition?
parvalbumin (PV) and somatostatin (SST) cells
feedback inhibition provides:
stability
feedback inhibition arises from:
local excitation in neural circuits (in contrast with feedforward inhibition which can be generated by long range excitation)
what is lateral inhibition?
one pyramidal cell activates an interneuron to inhibit another pyramidal cell
what types of cells mediate lateral inhibition?
somatostatin (SST) cells
lateral inhibition generates ______ between neural groups
segregation
without somatostatin (SST) cells, other pyramidal cells can:
fire when they aren’t supposed to
what is disinhibition?
inhibitory –> inhibitory cell connectivity, creating “net” excitation of another cell population (basically inhibiting the inhibitory cells)
the ______ connection is disinhibitory with respect to pyramidal cells
VIP –> SST
without vasoactive intestinal peptide (VIP), pyramidal cells:
fire less
what is volume inhibition?
neurogliaform cells release GABA and act on both GABA-B and GABA-A receptors
the effects of neurogliaform (NG) activation can be ______, therefore NG cells can influence activity in a _____ way
synaptic and extra-synaptic, non-synaptic (non-specific)
what is feedforward excitation?
excitatory cells mediate excitation of other neurons
an essential feature of communication within and between brain regions
feedforward excitation
connections between pyramidal cells is ______, so connectivity is relatively ______. however, most neurons are excitatory, so a small number of pyramidal cells can ______
~3-10%, infrequent, exert a lot of excitation
feedforward excitation is usually:
specific (neurons that “code” for one stimulus will communicate)
the thalamus excites _____ of the visual cortex
layer 4
can interneurons be excited by thalamic input?
yes
there is a strong positive correlation between ____ and ____
inhibition, excitation
small increases in the excitation:inhibition ratio generate:
action potentials
when you move, you generate:
“self-generated” sounds
why is it important for the brain to tune out “self-generated” sounds?
so that other sounds can be heard while moving
how does feedforward inhibition work with self-generated sounds?
- the motor cortex is activated during movement (running)
- excitatory neurons from the motor cortex activate PV itnerneurons in the auditory cortex
- PV interneurons suppress auditory cortex during movement
how does lateral inhibition work with surround suppression of the visual cortex?
pyramidal cells in layer V1 decrease their firing with larger stimuli that outside their receptive field, and SST interneurons increase their activity
surround suppression arises from:
lateral inhibition
surround suppression may participate in perceptual ability to:
recognize continuity of objects in the visual field
why do pyramidal cells prefer small stimuli?
because they are supressed by cells that like bigger stimuli (like SST interneurons)
during locomotion, V1 cells become:
active, even with no visual stimuli
VIP cells are activated during locomotion, which induces:
disinhibition of pyramidal cells
which neurotransmisster activates VIP cells?
acetylcholine
induces vasodilation and increases blood flow
vasoactive intestinal polypeptide (VIP)
induces vasoconstriction and decreases blood flow
somatostatin (SST)
describe the experiment to determine sync-fire chains
the preferred orientation of V1 cells was recorded. following the experiment, the same neurons were recorded in brain slices to test the connections between cells using patch clamp physiology
an immediate early gene that indicates neurons with high action potential firing rates
c-fos
following sleep, neurogliaform cells show:
c-fos in the cortex
neurogliaform cells may cause:
decreased cortical activity during sleep
