Amyloid Beta-Protein and Neural Network Dysfunction

Figure 1

The amyloid beta-peptide disrupts neural network activity along with cognition. The scheme in the middle represents a putative neural network containing neurons with different intrinsic properties (represented in different colors) that interact through synaptic connections (represented by lines). In the case of the hippocampal CA1 network the pyramidal cells, represented by the red circles, interact with each other but also with different populations of GABAergic interneurons, represented by the green and blue circles, to generate different patterns of population activity during cognitive processing. Of course, the generation of oscillatory activity by this network is required during normal cognitive processing (right, upper trace) [23–26, 37], whereas the alterations in such oscillatory activity (lower trace) produced by amyloid beta-protein have been associated with cognitive deficits [20, 21]. The question mark represents the current search for the cellular mechanisms underlying such disruption. The traces on the left are recordings of hippocampal oscillatory activity obtained in vitro before and after bath application of amyloid beta-protein 30 nM. The photographs at the top and bottom represent a mouse during a test session of the passive avoidance paradigm. During such a session, control animals tend to remain in the illuminated compartment due to the fact that on the previous day they received an electric shock in the dark compartment. Animals with disrupted memory tend to cross into the dark compartment, as already proven for amyloid beta-application in this paradigm [38, 39]. In summary, the figure represents the relationship between normal cognitive processing and the generation of specific neural network activities as well as the fact that amyloid beta-protein disrupts both of these interconnected processes.