This practical session involves exploring the mammalian brain through various resources and experiments. Key points covered include the organization and subdivisions of the cerebellum, differences between fish, primate, and human brains, structures like the corpus callosum and basal ganglia, diseases that impact movement like Huntington's and Parkinson's, the role of the hippocampus in spatial memory, adult neurogenesis in the hippocampus, Alzheimer's disease, brain mapping initiatives, and challenges in defining brain regions. Single-cell analysis is discussed as a way to reveal cell heterogeneity.

1. Practical session
Exploration of the mammalian brain
2022
Patrick PLA – Paris-Saclay University

4. Purves

6. Gilbert

11. https://en.wikipedia.org/wiki/L1_syndrome#/media/File:Cerebral_aqueduct_-_animation.gif

16. Organization and subdivisions of the cerebellum

22. This form of LTD has been implicated in the motor learning
that mediates the coordination, acquisition, and storage of
complex movements in the cerebellum.

26. Fish brain
Mesencephalon
(mid-brain)

27. Cortex is composed of 6 neuronal layers

29. Primates have bigger brains with a higher neuronal density

30. Source : https://www.hominides.com/html/dossiers/cerveau.php

36. Corpus callosum
Exists only in placental mammals
Largest white matter structure in the human brain, consisting of 200–300 million axonal projections
Genu (coral), premotor
(green), sensory-motor
(purple), parietal (pink),
temporal (yellow), and
splenium (blue).
For example, when simple written instructions
such as “laugh” or “walk” are presented visually to the
left visual field—and thus to the right brain—of a splitbrain patient, many subjects have
enough rudimentary verbal understanding in the right hemisphere to execute the
commanded action. However, when asked to report why they laughed or walked, they
typically confabulate a response using the superior language skills in the left
hemisphere, saying, for instance, that something the experimenter
said struck them as funny, or that they were tired of sitting and needed to walk a bit.
Thus, the same individual would appear, under these circumstances, to
harbor two relatively independent domains of awareness.
Purves

37. Basal ganglia

38. See :
http://www.youtube.com/watch?v=DccFiN5akCg
Two degenerative
diseases implicating
basal ganglia
In non pathological conditions, all arrows have the same width
(a) In Huntington’s disease, the inhibitory projection along the indirect
pathway from the striatum to the external segment of the globus pallidus
(GPe) is reduced. The net consequence is
reduced inhibitory output from the internal segment of the globus
pallidus (GPi) and thus an increase in cortical excitation and movement.
(b) Parkinson’s disease reduces inhibitory activity primarily alongthe
direct pathway, resulting in increased inhibition from the GPi to the
thalamus and thus a reduction
in cortical activity and movement.
GP = globus pallidus
SNc = substantia nigra
STN = noyau subthalamique

39. Huntington’s disease
Origin of CAG
triplet
mutations
Huntington’s disease

41. Control of movement

42. Hippocampus

43. (Purves)
Neurogenesis
in adult
mammalian
brain

44. Adult neurogenesis in the dentate gyrus of
the hippocampus
BrdU
(proliferation) DCX
(neuronal maturation)
NeuN
(mature neurons)

45. Hippocampus is
implicated in spatial
memory
Un rat va et vient le long d'une voie surélevée, s’arrêtant à chaque
extrémité pour manger une petite récompense de nourriture. Les
points indiquent les positions où les potentiels d'action ont été
enregistrés, les couleurs indiquant quel neurone de la couche CA1
de l’hippocampe a émis le potentiel d'action.
Implication de « cellules de lieu »

46. Alzheimer’s disease

47. Nissl staining (human) Nissl staining (mouse)
NeuN staining (marmoset)
https://doi.org/10.1146/annurev-neuro-100520-082639
Maps of the
mammalian
brain

48. Brain anatomical atlases are crucial for a wide range of applications :
• Fundamental investigations
• Defining stereotaxic coordinates
• Identifying patterns of neural activity associated with behaviour
• Integrating morphological, transcriptomics and neural activity data
• Comparison between species

49. Stereotaxic apparatus

51. Initiatives to develop atlases :
• Human cell atlas
(https://www.humancellatlas.org/)
• BRAIN initiative
(https://braininitiative.nih.gov/)
• Human brain projects
(https://www.humanbrainproject.eu/en/
/)
• Allen Brain Atlas

52. The natural variability in brain structure between individuals complicates the establishment
of strict neuroanatomical definitions, raising the question of what features should be
considered to define a brain region.
The establishment of the type of information (i.e., modality) and level of detail (i.e., resolution)
relevant for accurate and reproducible description of the tissue organization are central challenges
in brain mapping.
Four characteristics have been suggested to best define brain regions:
topography, function, architecture, connectivity
Challenges for brain mapping

53. https://portal.brain-map.org/
https://mouse.brain-map.org/
https://human.brain-map.org/
Allen Brain Map
(from Allen Institute, Seattle, WA)
14 petabytes (14.106 Gb) of data

54. Various scales of connections
https://doi.org/10.3389/fnins.2019.00897

55. Single-cell analysis
can reveal cell
heterogeneity
https://doi.org/10.1146/annurev-neuro-100520-082639

56. https://www.youtube.com/watch?v=oWPktWADlr4

57. https://www.youtube.com/watch?v=oWPktWADlr4

58. Proteins specific to neurotransmitters-
subtype neurons
Neurotransmitter of neuron Markers
Dopamine Tyrosine Hydroxylase, SLC6A3 (dopamine
transporter)
Glutamate Vesicular Glutamate transporters
(vGLUT1, vGLUT2)
Acetylcholine Choline acetyltransferase (ChAT)
Serotonin Tryptophan hydroxylase 1 and 2 (TPH1
and TPH2)
GABA Glutamate decarboxylase (GAD65
(encoded by GAD2) and GAD67 (encoded
by GAD1))

59. Using single cell RNAseq
for frozen samples
of human brain
https://www.youtube.com/watch?v=rNX1LopFFLA

61. Cell type nomenclature
https://www.youtube.com/watch?v=rNX1LopFFLA

62. The Allen Developing Mouse Brain Reference
Atlases were designed to:
1) Allow users to directly compare gene
expression patterns to an annotated
developmental atlas.
2) Provide templates for the creation of 3D
computer models of the developing mouse brain.
3) Serve as a neuroanatomical foundation for
informatics-based analysis tools

63. https://www.youtube.com/watch?v=F8UJ4DHl_Zw