31 research outputs found
Consensus Paper: Cerebellar Development
The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum
Cocaine-induced plasticity in the cerebellum of sensitised mice
Rationale Prior research has accumulated a substantial
amount of evidence on the ability of cocaine to produce
short- and long-lasting molecular and structural plasticity in
the corticostriatal-limbic circuitry. However, traditionally, the
cerebellum has not been included in the addiction circuitry,
even though growing evidence supports its involvement in the
behavioural changes observed after repeated drug
experiences.
Objectives In the present study, we explored the ability of
seven cocaine administrations to alter plasticity in the cerebellar
vermis.
Methods After six cocaine injections, one injection every
48 h, mice remained undisturbed for 1 month in their home
cages. Following this withdrawal period, they received a new
cocaine injection of a lower dose. Locomotion, behavioural
stereotypes and several molecular and structural cerebellar
parameters were evaluated.
Results Cerebellar proBDNF and mature BDNF levels were
both enhanced by cocaine. The high BDNF expression was
associated with dendritic sprouting and increased terminal size
in Purkinje neurons. Additionally, we found a reduction in
extracellular matrix components that might facilitate the subsequent
remodelling of Purkinje-nuclear neuron synapses.
Conclusions Although speculative, it is possible that these
cocaine-dependent cerebellar changes were incubated during
withdrawal and manifested by the last drug injection.
Importantly, the present findings indicate that cocaine is able
to promote plasticity modifications in the cerebellum of
sensitised animals similar to those in the basal ganglia.This work was supported by grants and fellowships:
Ministerio de EconomĂa y Competitividad [PSI2011- 29181],
FPI-PREDOC2009/05, FPU12/04059, PPF 2013 (13I087.01/1) and UJI
(P1.1B2011-42)
Experience-Dependent Plasticity and Modulation of Growth Regulatory Molecules at Central Synapses
Structural remodeling or repair of neural circuits depends on the balance between intrinsic neuronal properties and regulatory cues present in the surrounding microenvironment. These processes are also influenced by experience, but it is still unclear how external stimuli modulate growth-regulatory mechanisms in the central nervous system. We asked whether environmental stimulation promotes neuronal plasticity by modifying the expression of growth-inhibitory molecules, specifically those of the extracellular matrix. We examined the effects of an enriched environment on neuritic remodeling and modulation of perineuronal nets in the deep cerebellar nuclei of adult mice. Perineuronal nets are meshworks of extracellular matrix that enwrap the neuronal perikaryon and restrict plasticity in the adult CNS. We found that exposure to an enriched environment induces significant morphological changes of Purkinje and precerebellar axon terminals in the cerebellar nuclei, accompanied by a conspicuous reduction of perineuronal nets. In the animals reared in an enriched environment, cerebellar nuclear neurons show decreased expression of mRNAs coding for key matrix components (as shown by real time PCR experiments), and enhanced activity of matrix degrading enzymes (matrix metalloproteinases 2 and 9), which was assessed by in situ zymography. Accordingly, we found that in mutant mice lacking a crucial perineuronal net component, cartilage link protein 1, perineuronal nets around cerebellar neurons are disrupted and plasticity of Purkinje cell terminal is enhanced. Moreover, all the effects of environmental stimulation are amplified if the afferent Purkinje axons are endowed with enhanced intrinsic growth capabilities, induced by overexpression of GAP-43. Our observations show that the maintenance and growth-inhibitory function of perineuronal nets are regulated by a dynamic interplay between pre- and postsynaptic neurons. External stimuli act on this interaction and shift the balance between synthesis and removal of matrix components in order to facilitate neuritic growth by locally dampening the activity of inhibitory cues