Dr. Jackson FINAL

Question 1

What function does the claustrum serve?

Answer 1

sleep, attention, memory, consciousness

Question 2

What are the claustrum receptors and psychedelic drugs?

Answer 2

serotonin receptors: psilocybin
kappa opioid receptors: salvia

Question 3

Where is the claustrum located?

Answer 3

thin sheet of cells between the striatum/putamin and the insula

Question 4

Why is the claustrum difficult to stimulate directly?

Answer 4

hidden by surrounding axon white matter fiber tracts

Question 5

The claustrum has what percentage of cells of the cerebral cortex?

Where do the connections go?

Answer 5

<1%

BUT densely connected region

Axons from the claustrum were found to connect to the most frontal and most posterior parts of the cerebral cortex

claustrum connects to almost all cortical areas

Question 6

claustrum has the strongest bidirectional communication with

Answer 6

frontal cortex

Question 7

There is weak sensory cortex input to the

Answer 7

claustrum

Question 8

Which NT can project to the claustrum

Answer 8

serotonin, dopamine, and acetylcholine

Question 9

Each sensory/motor cortical regions provides input to different zones of the claustrum. Therefore, different claustrum regions receive

Claustrum outputs are predominantly blank, so they release blank and blank neurons

Answer 9

input from different cortical regions (sensory motor input is more dorsal, olfactory zone is more ventral)

glutamatergic, glutamate, depolarize

Question 10

In the claustrum, frontal cortical regions receive inputs from the

and more posterior regions receive inputs from the

Answer 10

dorsal claustrum

ventral claustrum

Question 11

Humans, cats, and primates have a pronounced connection with areas of the

Rodents have a pronounced connection with areas of the

Answer 11

visual cortex

pre motor areas of the frontal cortex (suggesting a role in motor control)

Question 12

Excitatory cells (~80%) can be classified into 2 major subgroups

Inhibitory claustrum cells appear to be similar to the cortex and express (blank), which different subtypes such as

Answer 12

type 1 (non spiny), do not typically fire AP bursts

type 2 (spiny), extensive dendrites and fire AP bursts in response to inputs

GABA, subtypes: parvalbumin, somatostatin, vasoactive intestinal polypeptide

Question 13

How does electrical activity of neurons in the cortex impact the activity of neurons in the claustrum?

(Experiment tied to this)

Answer 13

parvalbumin (PV) and excitatory pyramidal cells (ClaC cells)

findings
inputs to PV cells was stronger
detection of an inhib response was found in excitatory cells, with a longer latency after the stimulation. This implies feed forward inhibitory circuit

The cortex activates the contralateral claustrum and inhibits the ipsilateral claustrum

Question 14

The claustrum activation inhibits excitatory cells in the PFC. Explain

Answer 14

using optogenetics, the claustrum was activated while recording pyramidal (excitatory) or GABAergic (inhibitory) cells in the prefrontal cortex (PFC)

Average firing rate of pyramidal cells was suppressed, and average firing rate of interneurons was increased

Question 15

Claustrum cells generate cortical inhibition through what

Answer 15

exciting NPY interneurons

reducing cortical inhibition by inhibiting specific interneurons decreases the inhibitory response

*NOTE THAT claustrum neurons are mainly excitatory (glutamatergic), they project to the cortex and activate inhibitory interneurons (NPY, release GABA), these inhibit pyramidal cells

Question 16

During sleep, the effects of claustrum stimulation is similar to

Answer 16

spontaneous slow waves (which is essential for many functions such as learning and memory)

episodic memories are thought to be consolidated or stabilized during sleep
replay/reactivation of neurons during REM or slow wave sleep have BOTH been shown to participate in consolidation

Question 17

Shown by EEG, claustrum stim induces a blank during sleep

Answer 17

delta wave, and delta waves help consolidate memories

Question 18

What is psilocybin

Answer 18

active compound in magic mushrooms and acts through the activation of serotonergic 5HT2A receptors

causes hallucinations, euphoria, and changes in perception

claustrum neurons have dense expression of 5HT2a receptors

Question 19

Psilocybin increases

Answer 19

spine density (female mice) in prefrontal cortex

spine density reflects excitatory synaptic input

effect is long lasting for several weeks

prefrontal cortex receives dense input from the claustrum

Question 20

Does psilocybin increase or decrease claustrum activity

Answer 20

decrease

but increase cortical neuron activity

if claustrum facilitates feed forward inhib, then increase in cortical activity could be explained by actions of psilocybin on the claustrum

NORMALLY
Claustrum active → interneurons active → cortical activity suppressed

WITH PSILOCYBIN (disinhibition)
Psilocybin ↓ claustrum → ↓ inhibition → ↑ cortical activity

Question 21

Is the claustrum - cortical connectivity increased or decreased in Parkinson’s?

Answer 21

decreased

Question 22

Is the claustrum activity increased or decreased in epilepsy?

Answer 22

either

Question 23

Is the claustrum bigger or smaller in Schizophrenia and major depression?

Answer 23

smaller

Question 24

Claustrum activation using chemogenetics, rescues hypersensitivity in chronic pain. Describe the experiment behind this

Answer 24

CFA toxin injected into paw to induce pain

pain associated with pathological increase in neural firing in ACC

claustrum can suppress ACC

claustrum activity is reduced during chronic pain

poking paw with light touch normally does not evoke the withdrawal of the paw, BUT WITH CHRONIC PAIN, claustrum inhib, non painful stim can trigger pain or withdrawal (allodynia)

In some chronic pain conditions, claustrum activity is reduced, which may contribute to increased activity in pain-related cortical regions such as the ACC.

Question 25

What is NORSE?

Answer 25

new onset refractory status epilepticus rare condition healthy individual presents with epilepsy without a known cause claustrum lesion or fMRI hyperintensity is often found death can result, or chronic epilepsy

Question 26

Anatomical techniques to see neurons

Answer 26

Golgi stain method fills cells with silver chromate and appears black (Ramon y Cajal) fluorescent dyes can be used to label cells Both need neurons to be traced out either manually or with software

Question 27

Anatomical techniques to measure neurons

Answer 27

anterograde tracing neural connections (dyes, fluorescent proteins through axons to be visualized (AAV) retrograde tracing connections (dye or compound gets incorporated into the axon and travels backward to the cell body (cholera toxin, fast blue, AAVs, rabies)

Question 28

Neuron stimulation techniques:

Answer 28

electrical stim: place wire into brain tissue, pass current into tissue to depolarize neurons with electrode. easy, effect, precise activation, indirect, unintended activation, antidromic activation of post synaptic cells light stim (optogenetics): ChR2. rapid control of spike timing, specific neuron types activated, no unintended activation of nearby neurons in brain. light can change temp of neural tissue, must deliver light to brain with brain implants chemical stim (pharmacogenetics): designer receptor expressed in cells of interest using genetic approaches, receptor is designed to be activated by a SPECIFIC ligand/ specific but no precise control over the timing of activation patch clamp single cell stim: 2 single neurons recorded using intracellular tech. DEFINITIVE TEST OC CONNECTIVIY BETWEEN NEURONS, but challenging to implement, high failure rate, only useful for testing close connections

Question 29

Within a brain region, cells closed to each other are blank likely to connect to each other

Answer 29

more

Question 30

between brain regions, there is blank relation between distance and connectivity

Answer 30

no or weak

Question 31

Majority of cells are

Answer 31

excitatory, pyramidal, large in diameter, project locally to nearby cells and to different regions of the brain >0.2mm MANY DENDRITIC SPINES

Question 32

minority of cells are

Answer 32

inhibitory interneurons release GABA inhibit the post synaptic cell 10% of all neurons in cortex mainly project locally within 0.2mm generally lacking spines

Question 33

4 interneurons and their connections

Answer 33

parvalbumin (PV) calcium bidning protein: synapse of cell bodies, layer 2-6, GABA-A mediated inhib somatostatin (SST) peptide: synapse on dendrites, layer 2-6, GABA-A mediated inhib vasoactive intestinal polypeptide (VIP) peptide: synapse on OTHER interneurons, layer 1-3, GABA-A mediated inhib neuropeptide Y/neurogliaform cells (NG) nitric oxide synthase and neuropeptide Y: synapse on OTHER interneurons AND excitatory cells, layer 1-3, GABA B and volume transmission

Question 34

PV and SST cells both participate in

Answer 34

feedback inhibition

Question 35

Only PV cells mediate (usually)

Answer 35

feedforward inhibition

Question 36

What is lateral inhibition? What cells participate in this

Answer 36

one pyramidal cell activates an interneuron to inhibit another pyramidal cell SST cells mediate lateral inhib lateral inhib generates segregation between neural groups without SST cells, other pyramidal cells can fire when theyre not supposed to

Question 37

The VIP to SST connection is

Answer 37

disinhibitory with respect to pyramidal cells

Question 38

What is volume inhibition

Answer 38

neurogliaform cells release GABA, and act on GABA B receptors and GABA A receptor effects can be synaptic and extra synaptic NG cells can therefore influence activity in a non-synaptic way

Question 39

When you move, you generate self generated sounds. It is important for the brain to tune out these sounds so that other sounds can be heard while moving. What happens here?

Answer 39

motor cortex is activated during movement excitatory neurons from motor cortex activated PV interneurons in auditory cortex PV interneurons suppress auditory cortex during movement FEEDFORWARD INHIBITION

Question 40

Feedforward inhib uses

Answer 40

PV interneurons (inhib something)

Question 41

Surround suppression arises from

Answer 41

lateral inhibition pyramidal cells decrease firing to larger stim outside their receptive field (surround suppression) SST interneuron increases their activity

Question 42

During locomotion, V1 cells become active, even with no visual stimuli What cells are activated during locomotion?

Answer 42

VIP, by acetylcholine, which induces disinhib of pyramidal cells

Question 43

What does VIP and SST do to blood flow?

Answer 43

VIP induces vasodilation SST induces vasoconstriction

Question 44

What causes decreased cortical activity during sleep

Answer 44

neurogliaform c fos is an immediate early gene that indicates neurons with high AP firing rates following sleep, neurogliaform cells show c fos in cortex, other cell types do not show c fos