Cerebellar Development Flashcards
cerebellum
originates in the hindbrain (shown in lamprey studies)
folded into folia - rectilinear (has many perpendicular structures)
organisms vary in the number of cerebellar cells
functions of the cerebellum
motor coordination
fine control of movement & motor learning
comparator
proprioception
errors in the function of the cerebellum
posture
ataxia (abnormally coordinated muscle contractions)
intention tremor (movement activation delay e.g. parkinsonism tremor)
type of coordination used by the cerebellum
ipsilateral coordination (right cerebellum to right arm)
rhythmic sensorimotor synchronisation
feedforward control system in goldfish
anticipates an error which causes a function e.g. memory
cognitive disorders
cerebellar affective disorder - affects emotion/language/sensors
ASD - smaller/larger cerebellum
emotion & executive decision
cell types in the cerebellum
Purkinje cells
granule cells
inhibitory neurons (molecular layer interneurons/golgi cells)
deep cerebellar nuclei (fire APs)
cortical/outer layer architecture
molecular layer (many axons and dendrites)
Purkinje cells (output to deep nuclei)
granule cell (input from all areas)
2 forms of excitatory inputs
climbing fibres
mossy fibres
where are inhibitory projections sent to
inferior olive
what maps the regional boundaries of the cerebellum
isthmus (organiser) divides the mesencephalon from the hindbrain, separates MB from the HB, contributes to feathers, secretes FGF
Mapping the isthmus
with a surgical chimaera
Hallonet et al, 1990
swap brain regions between quail and chick embryo: Entire hindbrain (metencephalic vesicle) exchange, Half hindbrain exchange, Midbrain (diencephalic and mesencephalic vesicles) exchange
results: longitudinal movements stretch and distort the early neural tube, purkinje cells orginate from the same region as the ventricular epithelium
gene expression for isthmus positioning
increased Otx2 (MB) - deletion loses entire head
Gbx2 - positions isthmus
decreased Hoxa2
gap between otx2 and hoxa2 is where cerebellum appears (r1)
r1 - where all purkinje cells and granule cells form
what is the cerebellum derived from
Dorsal: dl1 Math1 (atoh1)
ventral: dl4/5 Ptf1a
bHLH (TF) genes in different DV domains
mapping granule cell origins with Math1 genetic fate map
Machold & Fishell , 2005
cross MATH1CreERT2 and R26R mice
tamoxifen activates lacZ and binds to ERT2 (estrogen R), cre activated, cre removes floxed stop sequence from lacZ, lacZ turned on, permanent B-gal expression
MATH1 controls cre
granule cells travel on surface then migrate inwards
