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Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR) dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked and it is believed that several crucial mechanisms still remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to the author’s knowledge it is the first time that SI methods are applied on electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse engineering of mGluR-LTD responses. It is suggested that such SI methods can aid to unravel the complexities of synaptic function.

Recent advances have started to uncover the underlying mechanisms of metabotropic glutamate receptor (mGluR) dependent long-term depression (LTD). However, it is not completely clear how these mechanisms are linked and it is believed that several crucial mechanisms still remain to be revealed. In this study, we investigated whether system identification (SI) methods can be used to gain insight into the mechanisms of synaptic plasticity. SI methods have shown to be an objective and powerful approach for describing how sensory neurons encode information about stimuli. However, to the author’s knowledge it is the first time that SI methods are applied on electrophysiological brain slice recordings of synaptic plasticity responses. The results indicate that the SI approach is a valuable tool for reverse engineering of mGluR-LTD responses. It is suggested that such SI methods can aid to unravel the complexities of synaptic function.

Germline mutations in SPRED1, a negative regulator of Ras, have been described in a neurofibromatosis type 1 (NF1)-like syndrome (NFLS) that included learning difficulties in some affected individuals. NFLS belongs to the group of phenotypically overlapping neurocardio-facial-cutaneous syndromes that are all caused by germ line mutations in genes of the Ras/mitogen-activated protein kinase extracellular signal-regulated kinase (ERK) pathway and that present with some degree of learning difficulties or mental retardation. We investigated hippocampus-dependent learning and memory as well as synaptic plasticity in Spred1-/-mice, an animal model of this newly discovered human syndrome. Spred1-/-mice show decreased learning and memory performance in the Morris water maze and visual-discrimination T-maze, but normal basic neuromotor and sensory abilities. Electrophysiological recordings on brain slices from these animals identified defects in short- and long-term synaptic hippocampal plasticity, including a disequilibrium between long-term potentiation (LTP) and long-term depression in CA1 region. Biochemical analysis, 4 h after LTP induction, demonstrated increased ERK-phosphorylation in Spred1-/-slices compared with those of wild-type littermates. This indicates that deficits in hippocampusdependent learning and synaptic plasticity induced by SPRED1 deficiency are related to hyperactivation of the Ras/ERK pathway. Copyright