γ-Aminobutyric Acid Type A Receptor Potentiation Inhibits Learning in a Computational Network Model

Background Propofol produces memory impairment at concentrations well below those abolishing consciousness. Episodic memory, mediated by the hippocampus, is most sensitive. Two potentially overlapping scenarios may explain how γ-aminobutyric acid receptor type A (GABAA) potentiation by propofol disrupts episodic memory—the first mediated by shifting the balance from excitation to inhibition while the second involves disruption of rhythmic oscillations. We use a hippocampal network model to explore these scenarios. The basis for these experiments is the proposal that the brain represents memories as groups of anatomically dispersed strongly connected neurons. Methods A neuronal network with connections modified by synaptic plasticity was exposed to patterned stimuli, after which spiking output demonstrated evidence of stimulus-related neuronal group development analogous to memory formation. The effect of GABAA potentiation on this memory model was studied in 100 unique networks. Results GABAA potentiation consistent with moderate propofol effects reduced neuronal group size formed in response to a patterned stimulus by around 70%. Concurrently, accuracy of a Bayesian classifier in identifying learned patterns in the network output was reduced. Greater potentiation led to near total failure of group formation. Theta rhythm variations had no effect on group size or classifier accuracy. Conclusions Memory formation is widely thought to depend on changes in neuronal connection strengths during learning that enable neuronal groups to respond with greater facility to familiar stimuli. This experiment suggests the ability to form such groups is sensitive to alteration in the balance between excitation and inhibition such as that resulting from administration of a γ-aminobutyric acid–mediated anesthetic agent.

Learning Polychronous Neuronal Groups Using Joint Weight-Delay Spike-Timing-Dependent Plasticity

Polychronous neuronal group (PNG), a type of cell assembly, is one of the putative mechanisms for neural information representation. According to the reader-centric definition, some readout neurons can become selective to the information represented by polychronous neuronal groups under ongoing activity. Here, in computational models, we show that the frequently activated polychronous neuronal groups can be learned by readout neurons with joint weight-delay spike-timing-dependent plasticity. The identity of neurons in the group and their expected spike timing at millisecond scale can be recovered from the incoming weights and delays of the readout neurons. The detection performance can be further improved by two layers of readout neurons. In this way, the detection of polychronous neuronal groups becomes an intrinsic part of the network, and the readout neurons become differentiated members in the group to indicate whether subsets of the group have been activated according to their spike timing. The readout spikes representing this information can be used to analyze how PNGs interact with each other or propagate to downstream networks for higher-level processing.

Computational Properties of Networks of Synchronous Groups of Spiking Neurons

We demonstrate a model in which synchronously firing ensembles of neurons are networked to produce computational results. Each ensemble is a group of biological integrate-and-fire spiking neurons, with probabilistic interconnections between groups. An analogy is drawn in which each individual processing unit of an artificial neural network corresponds to a neuronal group in a biological model. The activation value of a unit in the artificial neural network corresponds to the fraction of active neurons, synchronously firing, in a biological neuronal group. Weights of the artificial neural network correspond to the product of the interconnection density between groups, the group size of the presynaptic group, and the postsynaptic potential heights in the synchronous group model. All three of these parameters can modulate connection strengths between neuronal groups in the synchronous group models. We give an example of nonlinear classification (XOR) and a function approximation example in which the capability of the artificial neural network can be captured by a neural network model with biological integrate-and-fire neurons configured as a network of synchronously firing ensembles of such neurons. We point out that the general function approximation capability proven for feedforward artificial neural networks appears to be approximated by networks of neuronal groups that fire in synchrony, where the groups comprise integrate-and-fire neurons. We discuss the advantages of this type of model for biological systems, its possible learning mechanisms, and the associated timing relationships.