Lecture Kerkoerle

Question 1

Detailed neural mechanisms of top-down visual processing in macaque monkeys

Question 2

Cortical hierarchy

Answer 2

buttom-up stream in hirarchy

visual imput –> V1/V2 (spatial location) different neurons represent different features. –> V4 (larger receptive fields - more complex) differentiation in different elements (color, curved, rectilinear) –> TEO/TE –? vIPF

Question 3

Receptive fields

Answer 3

V1/V2 neurons in certain location that represent different visual elements (one location, differing neurons representing differing features). Neighbouring neurons that represent neighbouring locations in the visual field

Question 4

V4

Answer 4

larger receptive fields (more complex, i.e. circular or t-shaped) separation into several feature dimensions. I.e. Color, Curved, Rectilinerar

Question 5

TEO/TE

Answer 5

Visual fields become even bigger (entire objects, such as banana, apple, etc). Still division into several features (color, curved, rectilinear)

Question 6

vIPFC

Answer 6

completely abstract representations (i.e. circle, color, rectilinear,…)

Question 7

Artificial neural network (ANN)

Answer 7

convolutional neural network (filter)

Question 8

what is the directionality of the cortical hierarchy

Answer 8

it is actually 2-way, bottom-up is well understood, while top-down is not very well understood.

Question 9

selection of visual information in depression/schizophrenia, etc. iss impaired

Answer 9

First need to understand healthy functioning, to then understand what the impairment is

Question 10

How can top-down processing be investigated?

Answer 10

1. Laminar recordings
2. multi-photon imaging
3. distribution of cell types

Question 11

Why work with primates?

Answer 11

• primates are genetically vey similar to humans
• cell-types : genetic profile of important neurons (PVALB, SST, LAMPS, VIP)
• In macaque and Marmoset the expression level of these neurons shows high correlation with the human one
• translation is not possible if working with mouse or ferret

Question 12

How is the organization of macaque different to mouse

Answer 12

Anatomical connectivity between different areas with association cortex. In visual area there is a clear hierarchy.
Large network dissociated from sensory input, you can have internal representations, like working memory that is not affected by sensory imput

In the mouse there is almost no hierarchy, everything is more connected. less high level cognitive functions

Question 13

How is the columnal organization in V1 different between monkeys, mice and humans?

Answer 13

in V1 you have columnal organization, different orientations for different neurons which are clustered in macaque monkeys

but in rodents there is no such organization

Question 14

Monkeys vs humans

Answer 14

human- 3x bigger
V1 is relatively smaller in humans compared to macaque (prefrontal cortex has increased, but V1 is relatively shrunken.

This is not the case if you “count the neurons” –> in humans there is no difference to other monkeys.

Human cortex has increased in volume, but the number of neurons has not increased.

BUT- Neurons have become bigger

Basically, there is a different in degree, not in kind

it correlate in a difference in behavior (working memory)

Human capacity to memorize (ca. 4 elements), in monkeys for 2 items it already drops about 80%, this mean a monkey usually can only memorize about 1 element

Question 15

Laminar recording

Answer 15

Feedforward and feedback connections target separate cortical layers.

V1 : tracing individual axons

feedforward connections from LGN -> Layer 4A, L.4C, L.6

feedback connections: Axons coming from V1, arriving in L.1, L.2, and a little in L.3 and L.5 (avoids 4 and 6)

separate input coming in to the different layers (L4, L6 and L.3,L.5,L.1/2) in order to separate feedforward and feedback connections

Question 16

Laminar recordings in monkey V1

Answer 16

• Flash evoked activity
• presenting high contrast checkboard grading
• record simultaneously spiking activity across different layers

MUA

• normalization, all peaks are now 1 to see differences in time : L6 and L4 is a little bit earlier
• Synaptic input spreads very quickly, which is why it is hard to identify it

CSD: 2nd

spiking activity (action potentials)

LFP (corresponds to synaptic activity ) x2. subtract the neighbours

–> currents flowing away or towards the channel
current sink (where current flows inside neurons) - L4C - Feedforward

Question 17

LFP vs action potential

Answer 17

LFP: summed activity of a population of neurons (in Hz)

Action potentials: individual neural firing

Question 18

Selective attention task

Answer 18

4 possible targets
curve tracing task
monkey fixates a red dot. Then lines appear connecting red dot to one of 4 targets
Monkey has to follow curve and make eye movement to the target

First you record at the target, then the distractor

–> need for larger receptive fields
target vs distractor

Question 19

Spiking activity across layers

Answer 19

fixation (300 ms)
Stimulus (750 ms)
Saccade (monkey gets juice if correct)

if stimulus appears, there is a very strong response (peak) that can propagate to the next layer

Around 200 miliseconds: stabilizes in time.

Feedforward (no distinction between target and distractor)

only at about 200 milliseconds a distinction takes place

Question 20

Feedback laminar profile

Answer 20

MUS and cortical depth and CSD shows feedback in the correct layers

Question 21

Is V1 involved in working memory as well?

Answer 21

Stimulus 150 ms, but followed by delay so that monkey has to memorize.

Neurons in V1 still have modulation between target and distractor

There is working memory trace in V1 but lost if mask is presented

Working memory is only stored in prefrontal cortex

Question 22

Multi-photon imaging & activity-dependent fluorophores advantages

Answer 22

• sub-cellular resolution (ca. 2um)
• complete neural population
• map topography
• follow neurons over sessions (see same neuron and detect learning effect)
• connections between neurons/areas
• cell-type specificity
• image neuromodulators (e.g. dopamine)

link anatomy with congnitive functions

Question 23

Dissecting the neural microcircuit

Answer 23

A. Local somata and projections
Injection Site
Viral Expression

B. Cell-type specificity

C. Anterograde

D. Retrograde

You engineer a virus, it infects a cell and the cell starts producing any protein you want it to produce

local expression of virus

cell-type specific (inject virus anywhere and only specific neurons will be affected)

Viral vector technology

Question 24

Multi-photon microscopy

Answer 24

Light scattering–> overcome bad resolution

one photons vs 2 photons vs 3 photons excitation : the more light you get, the more signal you get

only at focal plane you get excitation

Question 25

multi-photoimaging in monkeys

Answer 25

visualizing neuronal connections using 2-photon imaging

Is there changing in V1

window implanted –> image axons and understand how they change while animal is learning the task.

Before learning and after learning axons changed while animal was learning

after a couple of weeks the dura grew back

if you have 3-photon imaging you can reach deeper

Question 26

Three-microscope suitable for macaque monkeys

Question 27

Imaging vasculature in monkey cortex

Question 28

Imaging neurons in monkey cortex

Answer 28

measure calcium activity

Question 29

2/ vs 3/photon imaging of the vasculature in the cortex through the dura

Answer 29

section the brain with light

Question 30

Distribution of cell types

Answer 30

Comparing hierarchies between mice and macaque monkeys

• cortical gradient of interneuron distribution

Feedforward -> conects to perimidal cells and PV cells

Feedback-> CR projecting to (inhibits) CB projecting to (disinhibiting) pyramidal

in macaque there is V2/V1 feedforward and ACC feedback

Mouse only has feedfarward processes

Question 31

Summary

Answer 31

• Selective attention involves feedback to V1
• Working memory involves feedback to V1, but working memory items are not stored in V1
• Three-photon microscopy allows imaging through natural dura in macaque monkeys
• Top-down circuits become dominant towards higher cortical areas, and this gradient is enhanced in macaque monkeys compared to mice
• This suggests that primates might have unique abilities to maintain internal goals and dynamically select information that is relevant for the task at hand