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Hippocampal synaptic and membrane function in the DBA/2J-mdx mouse model of Duchenne muscular dystrophy
Riccardo Bianchi1, Wouter Eilers2, Federica Pellati3
1University of Reading School of Pharmacy, Hopkins Building, Whiteknight Campus, Reading RG6 6LA, UK; University of Modena and Reggio Emilia, Department of Life Sciences, Via G. Campi 103-287, 41125 Modena, Italy.
Abstract:
Dystrophin deficiency is associated with alterations in cell physiology. The functional consequences of dystrophin deficiency are particularly severe for muscle physiology, as observed in Duchenne muscle dystrophy (DMD). DMD is caused by the absence of a 427 kDa isoform of dystrophin. However, in addition to muscular dystrophy symptoms, DMD is frequently associated with memory and attention deficits and epilepsy. While this may be associated with a role for dystrophin in neuronal physiology, it is not clear what neuronal alterations are linked with DMD. Our work shows that CA1 pyramidal neurons from DBA/2J-mdx mice have increased afterhyperpolarization compared to WT controls. All the other electrotonic and electrogenic membrane properties were unaffected by this genotype. Finally, basal synaptic transmission, short-term and long-term synaptic plasticity at Schaffer collateral to CA1 glutamatergic synapses were unchanged between mdx and WT controls. These data show that the excitatory component of hippocampal activity is largely preserved in DBA/2J-mdx mice. Further studies, extending the investigation to the inhibitory GABAergic function, may provide a more complete picture of the functional, network alterations underlying impaired cognition in DMD. In addition, the investigation of changes in neuronal single conductance biophysical properties associated with this genotype, is required to identify the functional alterations associated with dystrophin deficiency and clarify its role in neuronal function.
Insights
Dystrophin deficiency in Duchenne muscular dystrophy (DMD) affects brain function. This study found altered neuronal activity in the hippocampus of mdx mice, suggesting a role for dystrophin in cognitive processes.
Area of Science:
- Neuroscience
- Cell Physiology
- Genetics
Background:
- Dystrophin deficiency, observed in Duchenne muscular dystrophy (DMD), impacts muscle physiology.
- DMD is also linked to cognitive impairments, including memory and attention deficits, and epilepsy.
- The specific neuronal alterations underlying these cognitive deficits in DMD remain unclear.
Purpose of the Study:
- To investigate the electrophysiological properties of CA1 pyramidal neurons in DBA/2J-mdx mice.
- To assess synaptic transmission and plasticity in the hippocampus of mdx mice.
- To identify functional neuronal alterations associated with dystrophin deficiency.
Main Methods:
- Electrophysiological recordings of CA1 pyramidal neurons in DBA/2J-mdx and wild-type (WT) mice.
- Assessment of neuronal membrane properties, including afterhyperpolarization.
- Evaluation of basal synaptic transmission and synaptic plasticity at Schaffer collateral to CA1 synapses.
Main Results:
- CA1 pyramidal neurons in DBA/2J-mdx mice exhibited increased afterhyperpolarization compared to WT controls.
- Other electrotonic and electrogenic membrane properties of these neurons were unaffected by genotype.
- Basal synaptic transmission and both short-term and long-term synaptic plasticity were unchanged between mdx and WT mice.
Conclusions:
- The excitatory component of hippocampal activity is largely preserved in DBA/2J-mdx mice.
- Further investigation into inhibitory GABAergic function is needed for a complete understanding of cognitive impairments in DMD.
- Identifying changes in neuronal single conductance biophysical properties is crucial for clarifying dystrophin's role in neuronal function.
