Components of a circuit Flashcards

1
Q

Explain the layers and columns seen in the organisation of the brain (6)

A

Cortical column: - made up of 6 layers
- each signalling to different parts of the brain
- also known as the ‘unit of computation’
Layer 1: outside the brain, adjacent to pia mater
Layer 3 +5: main output of the cortex, made up of mainly pyramidal cells
Layer ‘7’: white matter of brain

Cerebral cortex = approx 2mm thick sheet of neuronal cell bodies

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2
Q

Describe the cytoarchitecture of the brain old vs new (4)

A

Brodmann outlined 52 areas - then divided them into granular and a granular cortex (old)

Granular: mainly primary sensory areas

Agranular/dysgranular: lack granular cells = primary motor cortex, frontal cortex and entorhinal cortex

So 6 layers of cortical column:
1 = Molecular
2 = External granular
3 = External pyramidal
4 = Internal granular
5 = Internal pyramidal
6 = Polymorphous

Modern functional imaging (based on function, architecture + connectivity) allows use to see 360 areas compared to 52 (new)

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3
Q

granular visual cortex vs agranular frontal cortex histology (2)

A

used immunohistochemistry

Granular visual cortex:
- distinct L4
- L3 + 5 clearly separated

agranular frontal cortex:
- no distinct L4
-L3 + L5 merged together
= need diff staining methods to see each layer

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4
Q

agranular vs dysgranular vs granular cortex (3)

A

Agranular: lacks true granular layer

Granular: has distinct L4 neurons, has a transitional cortex region, inputs + outputs come from the thalamus (=thalamocortical projections)

dysgranular: kind of present L4 region

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5
Q

Explain the variation in cortical laminar structure (4)

A

Eulaminate/ Granular areas: Cortical regions with a well developed 6 layer structure, including a prominent layer 4

Agranular/Differentiated areas: lack a layer 4 and have a complex laminar structure

Connectivity + synaptic specificity in eulaminate areas vary

projections target different layers depending on complexity of the area in question

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6
Q

Explain how the structural model predicts the degree of synaptic plasticity/stability (5)

A

-Researchers suggested that variability if architecture starts during development

  • limbic (learning+memory) areas develop earlier than eulaminate (complex) areas:
    limbic = plasticity and vulnerability
    Eulaminate = stability and less plasticity
  • cortical architecture correlates w/ synaptic plasticity - diverse expression of markers for neural stability and adaptability across cortex’s layers

(factors that limit synaptic plasticity=)Myelin content, PV neuron density, Perineuronal net density (increasing):
- agranular
- dysgranular
- Eulaminate I
- Eulaminate II

(factors that enhance synaptic plasticity=)CaMKII + GFAP expression (decreasing):
- agranular
- dysgranular
- Eulaminate I
- Eulaminate II

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7
Q

what can be said about less complex laminar/simple regions? (2)

A

less complex laminar structures show increased susceptibility to various neurological conditions, including neurodegeneration, disease, epilepsy, neurodevelopmental disorders

=implying that a link between this lamina simplicity and vulnerability causes more vulnerability

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8
Q

What is spatial transcriptomics? Why do we use it/benefit? (2)

A

It’s a single cell RNA sequencing technique and together with single molecule FISH it shows cell type heterogeneity.

This is beneficial to show the possible associate variations within the cortical structure - with all the variations in expression of the different genes.

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9
Q

Describe the benefit of single cell transcriptomics (2)

A

They actually showed an association between multiple genes and the structure of the cortex in different brain areas.

= now possible to associate variations within the cortical structure with variations in expression of different genes. So the description of the cortex has become more complicated as time has gone by

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10
Q

What spatial gene expression difference was found in DV axes? (3)

A

looked at the expression of potassium channels along different axes + different receptors.

= found was there’s differences from dorsal to ventral-> gradients underlie prominent heterogeneity of CA1 pyramidal neurons

-distinct difference in resting membrane + potential spike threshold b/w 2 regions

(which couldn’t see from just using NISSL staining)

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11
Q

What are the effects of genetic influences on human cortical structure? (4)

A

There are differences in area and enrichment.

  • Cortical structure was seen in MRI of 51665 individuals
  • the genomic location of associated loci was identified
  • after which enrichment was measured in the developing cortex
    –>expansion of cortical surface areas actually driven by proliferating neural progenitor cells
  • Finally concluded that genetic correlations with cortical surface area varies
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12
Q

Explain the functional organisation of the brain (lobes and cortices) (4+6)

A

4 lobes:
Frontal
Parietal
Occipital
Temporal

6 Cortices:
Motor cortex - FL
Sensory cortex - PL
Visual cortex - OL
Auditory cortex
Olfactory cortex
Gustatory cortex

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13
Q

What is the central sulcus? (1)

A

Central sulcus - dividing line b/w frontal + parietal lobe

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14
Q

Explain the neuron charge distribution in the cortical column (7)

A
  • Density increases as the layers increase (1= least, 6= most)
  • layer 1 = mostly Inhib
  • layer 2/3 = inhib
  • layer 3 = predom excitatory
  • layer 4 = inhib
  • layer 5 = predom excitatory
  • layer 6 = inhib
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15
Q

cortical column in mammals facts (2)

A
  • structures that are conserved throughout mammals + not unique to human beings
  • sensory cortices show somatotopic organisation
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16
Q

Explain the cortical column in rodent barrel cortex (whiskers) - 5 steps (5)

A

Sensory whiskers from rat project to the brain stem:
1) whisker
2) trigeminal nerve that projects to
3) principal trigeminal nucleus and spinal trigeminal nucleus
4) they project to posterior medical nucleus + ventral posterior medial nucleus of thalamus -> out to barrel cortex (neocortex)

17
Q

Describe the synaptic pathways for processing whiskers related sensory information in the rodent barrel cortex (4)

A

1) goes from whisker to cortex as seen in condensed flashcards

2) whiskers and barrels - barrel C2 is the sensory whisker

3) thalamocortical connectivity from VPM + POM (L6) to layer 4 + 1 respectively

4) Corticocortical connectivity is when the primary somatosensory barrel cortex works with the secondary somatosensory cortex and primary motor cortex

18
Q

Explain the connections between excitatory neurons in the cortical column (2)

A

Layer 1 mainly inhibitory = form synapses with dendrites on pyramidal cells in layer 5

Image

19
Q

Are all cortical microcircuits the same? VPM and POM to barrel cortex (3)

A

The projections to each of the barrel cortices vary

VPM- upper layer, L4 POM-deeper layer, L5

but we see that there is a small section of the barrel in which they both merge/overlap imports -> inputs seen as diff parts of the thalamus

20
Q

Explain the hippocampus’ cytoarchitecture (4)

A

pyramidal cells - major cell layer of hippo + main output layer to entorhinal cortex

striatum oriens- exclusively gabergic + fall into 3 subtypes:
-SP
-SR
-SLM
-trisynaogic canonical pathway

-has basket cells too

21
Q

how do you look at the hippocampal layers? (1)

A

Do a microdissection and carry out some biochemical tests to look at the different biochemical composition of the different layers

22
Q

Name the trisynaogic canonical pathway (7)

A

1) input
2) DC
3) CA3
4) CA1
5) output
6) subiculum
7) entorhinal cortex

23
Q

Excitatory neurons recap (3)

A
  • Uses glutamate as a neurotransmitter -> targets AMPA, NMDA and kainate ionotrophic receptors + mGluR’s
  • typically = pyramidal cells (L2,3,5,6) or Stellate cells (L4) or in striatum pyramidales (hippocampus)
  • sends projections within column to other cortical regions and to subcortical areas
24
Q

Inhibitory interneurons recap (6)

A
  • use GABA as neurotransmitter, target ionotrophic GABA A + B receptors
  • Found in all cortical layers

-Typically connect within a local circuit but long range GABAergic neuron’s also exist

  • comprise only 10-20% of all neurons in the brain
  • exert powerful influence over excitatory cells
  • numerous subtypes exist (each w/ unique specialisation to control specific aspects of cell function)
25
Q

What features can you use to characterise interneurons? (6)

A
  • firing/ electrophysiologival properties
  • morphology
  • axon projections and post-synaptic target
  • expression of neuropeptides/ calcium binding proteins
  • embryonic origin
  • location (cortical/hippocampal layer)
26
Q

Where are interneurons born and why does it matter? (2)

A

During dev, over 90% are born in the caudal ganglionic eminence or the medial ganglionic eminence

  • during this dev = subtypes are specified and they are organised into different brain areas

(=site of origin of the interneurons largely determines the spatial organisation of the biochemical characterisation of the different interneurons within the cortex. =Embryology leads to complexity in the neocortex and the spatial organisation of different types of interneurons)

27
Q

Explain the 3 main trisynaptic canonical circuit connections (3)

A

EC -> DG: via perforant path

DG -> CA3: via mossy fibres

CA3 -> CA: via Schaffer collaterals

28
Q

Why are interneurons important? (1)

A

they play a fundamental role in coordinating network activity

29
Q

What are the 3 main interneurons cell classes? (3 +2)

A

Perisomatic targeting neurons
Dendrite targeting neurons
Interneurons targeting neurons

more than one type of interneurons can fit into each class

Each class is based of the cell type/ compartment the axon of an interneurons targets

30
Q

Perisomatic targeting (2)

A

These neurons will synapse with the soma or axon initial segment of pyramidal cells

= tight control over the firing of pyramidal cells

31
Q

Dendrite targeting neurons (2)

A

Neurons that synapse with basal or shital dendrites of pyramidal cells

= controls which inputs are activated

32
Q

Interneuron targeting interneurons (2)

A
  • Most inhibit other interneurons + pyramidal cells
  • But some can do this preferentially - they can mediate disinhibition (conditioned stim vs disinhibition of stim)
33
Q

What are the most commonly used interneuron markers? (3)

A

Parvalbumin (PV): found in fast spiking Perisomatic targeting neurons eg PV basket cells or Axo-axonic cells or chandelier cells

Somatostatin (SST): found in dendrite targeting neurons eg OL-M or Martinotti cells

5HT3a-R/ Vasoactive-intestinal peptide (VIP): target other interneurons

Other markers: CCK, NPY, 5HT3A

34
Q

PV background (3)

A
  • Fast spiking interneurons
  • Play a key role in generating rhythmic network activity
  • Exert powerful influence over pyramidal cells
35
Q

SST neuron (4)

A
  • primarily target dendrites
  • O-A, O-LM neurons or martinotti cells (deeper layers of hippo)
  • may have role in selecting inputs in pyramidal and VIP interneurons
  • regular spiking, with a pronounced hyperpolarisation activated current
36
Q

What are some interneuron classification system limitations? (2)

A

Interneurons have a heterogenous phenotype: many PV are fast spiking, SST are regular spiking

  • some resists such classification eg hippocampal his traits field cells express both PV and SST -> dendrite targeting and fast spiking
37
Q

how do you overcome the limitation of interneuron heterogeneity? (4+1)

A

-current clamp
-whole cell patch clamping
-pharmacological targets to try and isolate out which type
electrophysiological output of interest
- functional characteristics

morphology can be similar but electrophysiological profiling and their biochemistry = distinct