Remme, M. | bioRxiv Science

bioRxiv2020

Hebbian plasticity in parallel synaptic pathways: A circuit mechanism for systems memory consolidation

Systems memory consolidation involves the transfer of memories across brain regions and the transformation of memory content. For example, declarative memories that transiently depend on the hippocampal formation are transformed into long-term memory traces in neocortical networks, and procedural memories are transformed within cortico-striatal networks. These consolidation processes are thought to rely on replay and repetition of recently acquired memories, but the cellular and network mechanisms that mediate the changes of memories are poorly understood. Here, we suggest that systems memory consolidation could arise from Hebbian plasticity in networks with parallel synaptic pathways -- two ubiquitous features of neural circuits in the brain. We explore this hypothesis in the context of hippocampus-dependent memories. Using computational models and mathematical analyses, we illustrate how memories are transferred across circuits and discuss why their representations could change. The analyses suggest that Hebbian plasticity mediates consolidation by transferring a linear approximation of a previously acquired memory into a parallel pathway. Our modelling results are further in quantitative agreement with lesion studies in rodents. Moreover, a hierarchical iteration of the mechanism yields power-law forgetting -- as observed in psychophysical studies in humans. The predicted circuit mechanism thus bridges spatial scales from single cells to cortical areas and time scales from milliseconds to years. Author summaryAfter new memories are acquired, they can be transferred over time into other brain areas -- a process called systems memory consolidation. For example, new declarative memories, which refer to the conscious memory of facts and events, depend on the hippocampus. Older declarative memories, however, also rely on neocortical networks. The cellular mechanisms underlying such a transfer are poorly understood. In this work, we show that a simple and in the brain ubiquitous connectivity pattern, combined with a standard learning rule, leads to gradual memory transfer. We illustrate our proposed mechanism in numerical simulations and mathematical analyses. At the neurophysiological level, our theory explains experimental findings on memory storage in the hippocampal formation when specific pathways between neural populations are disrupted. At the psychophysical level, we can account for the power-law forgetting curves typically found in humans. A consequence of the proposed model is that consolidated memories can yield faster responses because they are stored in increasingly shorter synaptic pathways between sensory and motor areas. By giving a mechanistic explanation of the consolidation process, we contribute to the understanding of the transfer of memories and the reorganization of memories over time.

neuroscience↗

bioRxiv2018

Soma-axon coupling configurations that enhance neuronal coincidence detection

Coincidence detector neurons transmit timing information by responding preferentially to concurrent synaptic inputs. Principal cells of the medial superior olive (MSO) in the mammalian auditory brainstem are superb coincidence detectors. They encode sound source location with high temporal precision, distinguishing submillisecond timing differences among inputs. We investigate computationally how dynamic coupling between the \"input\" region (soma and dendrite) and the spike-generating \"output\" region (axon and axon initial segment) can enhance coincidence detection in MSO neurons. To do this, we formulate a two-compartment neuron model and characterize extensively coincidence detection sensitivity throughout a parameter space of coupling configurations. We focus on the interaction between coupling configuration and two currents that provide dynamic, voltage-gated, negative feedback in subthreshold voltage range: sodium current with rapid inactivation and low-threshold potassium current, IKLT. These currents reduce synaptic summation and can prevent spike generation unless inputs arrive with near simultaneity. We show that strong soma-to-axon coupling promotes the negative feedback effects of sodium inactivation and is, therefore, advantageous for coincidence detection. Furthermore, the \"feedforward\" combination of strong soma-to-axon coupling and weak axon-to-soma coupling enables spikes to be generated efficiently (few sodium channels needed) and with rapid recovery that enhances high-frequency coincidence detection. These observations detail the functional benefit of the strongly feedforward configuration that has been observed in physiological studies of MSO neurons. We find that IKLT further enhances coincidence detection sensitivity, but with effects that depend on coupling configuration. For instance, in weakly-coupled models, IKLT in the spike-generator compartment enhances coincidence detection more effectively than IKLT in the input compartment. By using a minimal model of soma-to-axon coupling, we connect structure, dynamics, and computation. Here, we consider the particular case of MSO coincidence detectors. In principle, our method for creating and exploring a parameter space of two-compartment models can be applied to other neurons.\n\nAuthor summaryBrain cells (neurons) are spatially extended structures. The locations at which neurons receive inputs and generate outputs are often distinct. We formulate and study a minimal mathematical model that describes the dynamical coupling between the input and output regions of a neuron. We construct our model to reflect known properties of neurons in the auditory brainstem that play an important role in our ability to locate sound sources. These neurons are known as \"coincidence detectors\" because they are most likely to respond when they receive simultaneous inputs. We use simulations to explore coincidence detection sensitivity throughout the parameter space of input-output coupling and to identify the coupling configurations that are best for neural coincidence detection. We find that strong forward coupling (from input region to output region), enhances coincidence detection sensitivity in our model and that low-threshold potassium current further improves coincidence detection. Our study is significant in that we detail how cell structure affects neuronal dynamics and, consequently, the ability of neurons to perform as temporally-precise coincidence detectors.

neuroscience↗