Electrophysiological studies on the hippocampus and prefrontal cortex assessing the effects of amyloidosis in amyloid precursor protein 23 transgenic mice.
In vitro and in vivo electrophysiological studies were done to investigate the neuronal function of the hippocampus and prefrontal cortex in the amyloid precursor protein (APP) 23 transgenic mouse model for amyloidosis developed by Sturchler-Pierrat et al. [Proc Natl Acad Sci USA 94 (1997) 13287]. Brain slices were taken from 3, 6, 9, 12, 18 and 24 month old wildtype and hemizygous type APP23 mice. Extracellular field potentials were recorded from the CA1 region of the hippocampus while stimulating the Schaffer collaterals. In addition, extracellular field potentials were elicited from areas within layer V/VI of the prefrontal cortex by stimulating the same layer V/VI. Basic synaptic function in the hippocampus was reduced in hemizygous APP23 mice compared with their wildtype littermates at 12 and 18 months of age, whereas, it was unaltered within the prefrontal cortex. Long-term potentiation in the hippocampus and the prefrontal cortex of hemizygous APP23 mice was similar compared with their wildtype littermates. In vivo electrophysiological experiments were done in 3, 9, 18 and 24 month old wildtype and hemizygous APP23 mice. No differences were observed in the number of single spontaneously active units recorded within the prefrontal cortex of hemizygous APP23 mice compared with their wildtype littermates. Field potentials elicited during stimulation of cortico-cortical pathways to assess synaptic transmission and short-term synaptic plasticity were also unchanged in hemizygous APP23 mice. Furthermore, presumable antidromic field potentials recorded in the prefrontal cortex during stimulation of the striatum were similar between the hemizygous APP23 and wildtype mice at each age. The present study shows that amyloidosis impairs basic synaptic function but not long-term potentiation in the hippocampus, however, does not alter any of the neurophysiological functions measured within the prefrontal cortex. These findings suggest that amyloidosis may be involved in altering some neurophysiological functions within only certain brain structures. Although APP23 mice have impaired cognitive performance, long-term plasticity, a cellular model for memory, is not affected, raising the question on the relationship between these processes.
Roder
S
S
Novartis Pharma Inc., Nervous System Research, CH-4002 Basel, Switzerland.
Danober
L
L
Pozza
M F
MF
Lingenhoehl
K
K
Wiederhold
K-H
KH
Olpe
H-R
HR
D000200:Action Potentials; D000367:Age Factors; D000544:Alzheimer Disease / Q000503:physiopathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000686:Amyloidosis / Q000503:physiopathology*; D000818:Animals; D004195:Disease Models, Animal; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000503:physiopathology*; D017774:Long-Term Potentiation; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons; D017397:Prefrontal Cortex / Q000503:physiopathology*; D009435:Synaptic Transmission
D016564:Amyloid beta-Protein Precursor