In the field’s current focus to understand what might go wrong at synapses early on in AD, measuring long-term potentiation has become a widely applied tool. This phenomenon of synaptic strengthening in response to intense stimulation via NMDA receptors is thought to underlie learning and memory. The jury on that question is still out, but LTP and related measurements have become widely accepted as a sensitive method of characterizing changes in synaptic function. Consequently, a growing number of labs have imported this technique into their study of AD mouse models.
Natasha Shinsky and colleagues at Elan Pharmaceuticals in South San Francisco yesterday presented a technical twist on this approach by using a microelectrode array developed by a German company to record simultaneously from 60 channels placed all over the mouse hippocampus. While this does not in itself improve the information one receives from each recorded field, the simultaneous data gathered from multiple points can be analyzed to better understand the response from the whole system rather than from just the one spot surrounding the recording electrode.
Shinksy, with Karen Chen and others, studied PDAPP mice at two time points: at five to seven months, when they have not deposited plaques yet, and at 18 to 20 months, when plaques litter the mice’s brains. Much previous work on mice models has focused on neuronal loss (i.e., its absence) and degeneration. Recent work, in Lennart Mucke’s, Frank LaFerla’s, and Dominic Walsh’s labs, for example, hints at LTP changes prior to plaque deposition. Yet, it is not clear how that relates to cognitive deficits (see, for example, Dewachter et al., 2002).
Shinksy measured basic synaptic transmission, paired-pulse ratio, and LTP induced in two different ways. Slices of five-month-old mice showed significant impairment in only one of these measures, namely LTP induced with high-frequency stimulation. The old mice showed alterations in all parameters measured. Taken together, this suggests that PDAPP mice have problems controlling transmitter release, probably develop internal calcium overload as a result of disturbed calcium homeostasis, have abnormal inhibition by the neurotransmitter GABA, and fewer synaptic sites than nontransgenic mice, the authors propose.—Gabrielle Strobel
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- Dewachter I, Reversé D, Caluwaerts N, Ris L, Kuipéri C, Van den Haute C, Spittaels K, Umans L, Serneels L, Thiry E, Moechars D, Mercken M, Godaux E, Van Leuven F. Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci. 2002 May 1;22(9):3445-53. PubMed.
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