Untersuchungen zur Bedeutung des Schizophrenie-assoziierten Genes ErbB4 während der Entwicklung cortikaler Mikroschaltkreise und der Funktion glutamaerger Synapsen
Final Report Abstract
In summary, these results show that a deletion of the schizophrenia-linked gene ErbB4 in SOM+ neurons changes the glutamatergic synaptic transmission onto SOM+ neurons of the thalamic reticular nucleus. ErbB4 deficiency specifically and selectively enhanced the strength of CT-TRN, but not TC-TRN synapses. I could show for the first time that selectively changing the CT-synaptic transmission onto TRN neurons influences the performance of mice in attention tasks. I found that strengthening of the CT-TRN synapses in the SOM/ErbB4 deficient mice resulted in an increased ability of the mice to select trained auditory stimuli in a background of distracting tones in the so-called "distracter" task. The advantage of the SOM/ErbB4 deficient mice was not only demonstrated by an increased accuracy, but also by a reduced reaction time compared to the wildtype littermates. This and the finding that the general hearing abilities in the mice were not changed, supports the assertion that the behavioral effect observed in the "distracter" task really reflects a change in attention. Preliminary data, showing that silencing of SOM+ TRN neurons using the neuronal silencer hM4Di leads to a decrease in the performance of mice in the "distracter" task, further evidences the importance of the TRN in attention. However, the SOM/ErbB4 deficient mice show a decrease in their performance in a rule selection task that requires responding to conflicting information from trained auditory and visual stimuli, suggesting that TRN neurons control different aspects of attention. Although strengthening of the CT-TRN synapses might be beneficial for solving some specific tasks, it can be rather disturbing for others. Further experiments, including in vivo recordings of TRN neurons in mice performing the attention tasks, would be required to investigate, how the TRN neurons function within the cortico-TRN-thalamic circuit during this different attentional demands.
Publications
- ErbB4 modulates attention by controlling synapse development in the reticular nucleus of the thalamus. 5th Meeting on Synapses: From Molecules to Circuits & Behavior, April 2011, Cold Spring Harbor, NY, USA
S. Ahrens, S. Jaramillo, H. Taniguchi, J. Z. Huang, C. Lai, B. Li
- ErbB4 modulates attention by controlling synapse development in the reticular nucleus of the thalamus. Meeting of the Society for Neuroscience, November 2011, Washington DC, USA
S. Ahrens, S. Jaramillo, H. Taniguchi, J. Z. Huang, C. Lai, B. Li
