DYT1 dystonia increases risk taking in humans

It has been difficult to link synaptic modification to overt behavioral changes. Rodent models of DYT1 dystonia, a motor disorder caused by a single gene mutation, demonstrate increased long-term potentiation and decreased long-term depression in corticostriatal synapses. Computationally, such asymmetric learning predicts risk taking in probabilistic tasks. Here we demonstrate abnormal risk taking in DYT1 dystonia patients, which is correlated with disease severity, thereby supporting striatal plasticity in shaping choice behavior in humans.

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Chemistry and Pharmacology of Long Term Potentiation: Contributions Beyond Synaptic Modification

10.21236/ada379775 ◽

2000 ◽

Author(s):

Gary Lynch ◽

M. Kessler

Keyword(s):

Long Term Potentiation ◽

Synaptic Modification ◽

Term Potentiation

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Long-Term Potentiation of Synaptic Transmission in the Hippocampus Obeys Hebb’s Rule for Synaptic Modification

Cellular Mechanisms of Conditioning and Behavioral Plasticity ◽

10.1007/978-1-4757-9610-0_6 ◽

1988 ◽

pp. 47-55 ◽

Cited By ~ 3

Author(s):

Holger Wigström ◽

Bengt Gustafsson ◽

Yan-You Huang

Keyword(s):

Synaptic Transmission ◽

Long Term Potentiation ◽

Synaptic Modification ◽

Term Potentiation

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Plasticity of the Synaptic Modification Range

Journal of Neurophysiology ◽

10.1152/jn.00164.2007 ◽

2007 ◽

Vol 98 (6) ◽

pp. 3688-3695 ◽

Cited By ~ 85

Author(s):

M.-S. Rioult-Pedotti ◽

J. P. Donoghue ◽

A. Dunaevsky

Keyword(s):

Long Term Potentiation ◽

Skill Learning ◽

Range Shift ◽

Synaptic Modification ◽

Term Potentiation ◽

Initial Learning ◽

Long Term Retention ◽

Activity Dependent ◽

Synaptic Responses

Activity-dependent synaptic plasticity is likely to provide a mechanism for learning and memory. Cortical synaptic responses that are strengthened within a fixed synaptic modification range after 5 days of motor skill learning are driven near the top of their range, leaving only limited room for additional synaptic strengthening. If synaptic strengthening is a requisite step for acquiring new skills, near saturation of long-term potentiation (LTP) should impede further learning or the LTP mechanism should recover after single-task learning. Here we show that the initial learning-induced synaptic enhancement is sustained even long after training has been discontinued and that the synaptic modification range shifts upward. This range shift places increased baseline synaptic efficacy back within the middle of its operating range, allowing prelearning levels of LTP and long-term depression. Persistent synaptic strengthening might be a substrate for long-term retention in motor cortex, whereas the shift in synaptic modification range ensures the availability for new synaptic strengthening.

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Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum

eLife ◽

10.7554/elife.33331 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 18

Author(s):

Marta Maltese ◽

Jennifer Stanic ◽

Annalisa Tassone ◽

Giuseppe Sciamanna ◽

Giulia Ponterio ◽

...

Keyword(s):

Clinical Manifestations ◽

Long Term Potentiation ◽

Motor Memory ◽

Childhood And Adolescence ◽

Synaptic Homeostasis ◽

Dyt1 Dystonia ◽

Abnormal Movements ◽

Term Potentiation ◽

Mushroom Spines

The onset of abnormal movements in DYT1 dystonia is between childhood and adolescence, although it is unclear why clinical manifestations appear during this developmental period. Plasticity at corticostriatal synapses is critically involved in motor memory. In the Tor1a+/Δgag DYT1 dystonia mouse model, long-term potentiation (LTP) appeared prematurely in a critical developmental window in striatal spiny neurons (SPNs), while long-term depression (LTD) was never recorded. Analysis of dendritic spines showed an increase of both spine width and mature mushroom spines in Tor1a+/Δgag neurons, paralleled by an enhanced AMPA receptor (AMPAR) accumulation. BDNF regulates AMPAR expression during development. Accordingly, both proBDNF and BDNF levels were significantly higher in Tor1a+/Δgag mice. Consistently, antagonism of BDNF rescued synaptic plasticity deficits and AMPA currents. Our findings demonstrate that early loss of functional and structural synaptic homeostasis represents a unique endophenotypic trait during striatal maturation, promoting the appearance of clinical manifestations in mutation carriers.

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