The impact of cortical deafferentation on the neocortical slow oscillation.

Slow oscillation is the main brain rhythm observed during deep sleep in mammals. Although several studies have demonstrated its neocortical origin, the extent of the thalamic contribution is still a matter of discussion. Using electrophysiological recordings in vivo on cats and computational modeling, we found that the local thalamic inactivation or the complete isolation of the neocortical slabs maintained within the brain dramatically reduced the expression of slow and fast oscillations in affected cortical areas. The slow oscillation began to recover 12 h after thalamic inactivation. The slow oscillation, but not faster activities, nearly recovered after 30 h and persisted for weeks in the isolated slabs. We also observed an increase of the membrane potential fluctuations recorded in vivo several hours after thalamic inactivation. Mimicking this enhancement in a network computational model with an increased postsynaptic activity of long-range intracortical afferents or scaling K(+) leak current, but not several other Na(+) and K(+) intrinsic currents was sufficient for recovering the slow oscillation. We conclude that, in the intact brain, the thalamus contributes to the generation of cortical active states of the slow oscillation and mediates its large-scale synchronization. Our study also suggests that the deafferentation-induced alterations of the sleep slow oscillation can be counteracted by compensatory intracortical mechanisms and that the sleep slow oscillation is a fundamental and intrinsic state of the neocortex.

A spiking network model of decision making employing rewarded STDP.

Reward-modulated spike timing dependent plasticity (STDP) combines unsupervised STDP with a reinforcement signal that modulates synaptic changes. It was proposed as a learning rule capable of solving the distal reward problem in reinforcement learning. Nonetheless, performance and limitations of this learning mechanism have yet to be tested for its ability to solve biological problems. In our work, rewarded STDP was implemented to model foraging behavior in a simulated environment. Over the course of training the network of spiking neurons developed the capability of producing highly successful decision-making. The network performance remained stable even after significant perturbations of synaptic structure. Rewarded STDP alone was insufficient to learn effective decision making due to the difficulty maintaining homeostatic equilibrium of synaptic weights and the development of local performance maxima. Our study predicts that successful learning requires stabilizing mechanisms that allow neurons to balance their input and output synapses as well as synaptic noise.

Heterosynaptic plasticity prevents runaway synaptic dynamics.

Spike timing-dependent plasticity (STDP) and other conventional Hebbian-type plasticity rules are prone to produce runaway dynamics of synaptic weights. Once potentiated, a synapse would have higher probability to lead to spikes and thus to be further potentiated, but once depressed, a synapse would tend to be further depressed. The runaway synaptic dynamics can be prevented by precisely balancing STDP rules for potentiation and depression; however, experimental evidence shows a great variety of potentiation and depression windows and magnitudes. Here we show that modifications of synapses to layer 2/3 pyramidal neurons from rat visual and auditory cortices in slices can be induced by intracellular tetanization: bursts of postsynaptic spikes without presynaptic stimulation. Induction of these heterosynaptic changes depended on the rise of intracellular calcium, and their direction and magnitude correlated with initial state of release mechanisms. We suggest that this type of plasticity serves as a mechanism that stabilizes the distribution of synaptic weights and prevents their runaway dynamics. To test this hypothesis, we develop a cortical neuron model implementing both homosynaptic (STDP) and heterosynaptic plasticity with properties matching the experimental data. We find that heterosynaptic plasticity effectively prevented runaway dynamics for the tested range of STDP and input parameters. Synaptic weights, although shifted from the original, remained normally distributed and nonsaturated. Our study presents a biophysically constrained model of how the interaction of different forms of plasticity--Hebbian and heterosynaptic--may prevent runaway synaptic dynamics and keep synaptic weights unsaturated and thus capable of further plastic changes and formation of new memories.

Non-homogeneous extracellular resistivity affects the current-source density profiles of up-down state oscillations.

Rhythmic local field potential (LFP) oscillations observed during deep sleep are the result of synchronized electrical activities of large neuronal ensembles, which consist of alternating periods of activity and silence, termed 'up' and 'down' states, respectively. Current-source density (CSD) analysis indicates that the up states of these slow oscillations are associated with current sources in superficial cortical layers and sinks in deep layers, while the down states display the opposite pattern of source-sink distribution. We show here that a network model of up and down states displays this CSD profile only if a frequency-filtering extracellular medium is assumed. When frequency filtering was modelled as inhomogeneous conductivity, this simple model had considerably more power in slow frequencies, resulting in significant differences in LFP and CSD profiles compared with the constant-resistivity model. These results suggest that the frequency-filtering properties of extracellular media may have important consequences for the interpretation of the results of CSD analysis.