A Biologically Plausible Model of Associative Memory Which Uses Disinhibition Rather Than Long-Term Potentiation

The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of Aβ and/or Tau.

Download Full-text

Cholecystokinin release triggered by NMDA receptors produces LTP and sound–sound associative memory

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1816833116 ◽

2019 ◽

Vol 116 (13) ◽

pp. 6397-6406 ◽

Cited By ~ 3

Author(s):

Xi Chen ◽

Xiao Li ◽

Yin Ting Wong ◽

Xuejiao Zheng ◽

Haitao Wang ◽

...

Keyword(s):

Associative Learning ◽

Associative Memory ◽

High Frequency ◽

Low Frequency ◽

Long Term Potentiation ◽

High Frequency Stimulation ◽

Low Frequency Stimulation ◽

Term Potentiation ◽

Frequency Stimulation

Memory is stored in neural networks via changes in synaptic strength mediated in part by NMDA receptor (NMDAR)-dependent long-term potentiation (LTP). Here we show that a cholecystokinin (CCK)-B receptor (CCKBR) antagonist blocks high-frequency stimulation-induced neocortical LTP, whereas local infusion of CCK induces LTP. CCK−/−mice lacked neocortical LTP and showed deficits in a cue–cue associative learning paradigm; and administration of CCK rescued associative learning deficits. High-frequency stimulation-induced neocortical LTP was completely blocked by either the NMDAR antagonist or the CCKBR antagonist, while application of either NMDA or CCK induced LTP after low-frequency stimulation. In the presence of CCK, LTP was still induced even after blockade of NMDARs. Local application of NMDA induced the release of CCK in the neocortex. These findings suggest that NMDARs control the release of CCK, which enables neocortical LTP and the formation of cue–cue associative memory.

Download Full-text

LEARNING IN AN OSCILLATORY CORTICAL MODEL

Fractals ◽

10.1142/s0218348x03001951 ◽

2003 ◽

Vol 11 (supp01) ◽

pp. 291-300

Author(s):

SILVIA SCARPETTA ◽

ZHAOPING LI ◽

JOHN HERTZ

Keyword(s):

Associative Memory ◽

Hebbian Learning ◽

Learning Rule ◽

Long Term Potentiation ◽

Activation Function ◽

Cortical Model ◽

Memory State ◽

Term Potentiation ◽

Conventional Models

We study a model of generalized-Hebbian learning in asymmetric oscillatory neural networks modeling cortical areas such as hippocampus and olfactory cortex. The learning rule is based on the synaptic plasticity observed experimentally, in particular long-term potentiation and long-term depression of the synaptic efficacies depending on the relative timing of the pre- and postsynaptic activities during learning. The learned memory or representational states can be encoded by both the amplitude and the phase patterns of the oscillating neural populations, enabling more efficient and robust information coding than in conventional models of associative memory or input representation. Depending on the class of nonlinearity of the activation function, the model can function as an associative memory for oscillatory patterns (nonlinearity of class II) or can generalize from or interpolate between the learned states, appropriate for the function of input representation (nonlinearity of class I). In the former case, simulations of the model exhibits a first order transition between the "disordered state" and the "ordered" memory state.

Download Full-text