bioRxiv Science⌕ Search

bioRxiv · 10.1101/346478

Principles Underlying the Input-Dependent Formation and Organization of Memories

Abstract

The brain of higher-order animals continuously and dynamically learns and adapts according to variable, complex environmental conditions. For this, the neuronal system of an agent exhibits the remarkable ability to dynamically store and organize the information of plenty of different environmental stimuli into a web of memories, which is essential for the generation of complex behaviors. The basic structures of this web are the functional organizations between two memories such as discrimination, association, and sequences. However, how these basic structures are formed robustly in an input-dependent manner by the underlying, complex and high-dimensional neuronal and synaptic dynamics is still unknown. Here, we develop a mathematical framework which reduces the complexity in several stages such that we obtain a low-dimensional mathematical description. This provides a direct link between the involved synaptic mechanisms, determining the neuronal and synaptic dynamics of the network, with the ability of the network to form diverse functional organizations. Given two widely-known synaptic mechanisms, correlation-based synaptic plasticity and homeostatic synaptic scaling, we use this new framework to identify that the interplay of these mechanisms enables the reliable formation of sequences and associations between two memory representations - missing the important functional organization of discrimination. We can show that this shortcoming can be compensated by considering a third mechanism as inhibitory synaptic plasticity. Thus, the here-presented framework and results provide a new link between diverse synaptic mechanisms and emerging functional organizations of memories. Furthermore, given our mathematical framework, one can now investigate the principles underlying the formation of the web of memories.\n\nAUTHOR SUMMARYHigher-order animals are permanently exposed to a variety of environmental inputs which have to be processed and stored such that the animal can react appropriate. Thereby, the ongoing challenge for the neuronal system is to continuously store novel and meaningful stimuli and, dependent on their content, to integrate them into the existing web of knowledge or memories. The smallest organizational entity of such a web of memories is described by the functional relation of two interconnected memories: They can be either unrelated (discrimination), mutually related (association), or uni-directionally related (sequence). However, the neuronal and synaptic dynamics underlying the formation of such structures is mainly unknown. To investigate possible links between physiological mechanisms and the organization of memories, in this work, we develop a general mathematical framework enabling analytical approach. Thereby, we show that the well-known mechanisms of synaptic plasticity and homeostatic scaling in conjunction with inhibitory synaptic plasticity enables the reliable formation of all basic relations between two memories. This work provides a further step in the understanding of the complex dynamics underlying the organization of knowledge in neural systems.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Herpich, J., Tetzlaff, C.. 2018-06-15. Principles Underlying the Input-Dependent Formation and Organization of Memories. https://doi.org/10.1101/346478

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Novel Tau Interaction Partners as Potential Biomarkers and Therapeutic Targets in Neurodegenerative Diseases

Alzheimers disease is a progressive neurodegenerative disorder leading to cognitive decline and ultimately death. One of the main hallmarks of this disease is the accumulation of pathological tau protein into neurofibrillary tangles. To better understand these pathological mechanisms, it is essential to characterize the tau protein interactome in health and disease. In this study, we performed a yeast two-hybrid screening using a human brain cDNA library, from which we identified 15 novel tau-interacting proteins that bind to full-length human tau, or its fragments: the N-terminus, microtubule-binding domain, or C-terminus. We subsequently validated these novel interactions using in vitro co-immunoprecipitation and colocalization assays with both physiological and pathological tau isoforms. Furthermore, their interactions with the human tau protein were analyzed using surface plasmon resonance. Finally, an in silico interactome analysis of these newly discovered tau-binding partners revealed several additional interactors that can link them to downstream processes critical to neurodegenerative pathways Our findings offer fresh insights into tau biology and highlight novel targets for therapeutic intervention and biomarker development.

neuroscience↗

Early visual cortex is not functionally necessary for temporal attention: A TMS study

Temporal attention enhances the selective processing of information at a specific point in time and improves perception. Previous neuroimaging studies investigating its neural mechanisms have either conflated temporal attention with temporal expectation or provided correlational evidence. Thus, whether early visual cortex is functionally necessary for temporal attention remains unknown. Here, we combined psychophysics with transcranial magnetic stimulation (TMS) to examine whether V1/V2 are functionally necessary and play a causal role in temporal attention. Observers performed an orientation-discrimination task in which two consecutive stimuli, T1 and T2, were presented in the periphery, preceded by a precue providing either valid or neutral temporal information. Double-pulse TMS was delivered under four conditions: at T1 (T1-TMS), at T2 (T2-TMS), at both T1 and T2 (both-TMS), or not at all (none-TMS), to assess its effects on temporal attention and the efficacy of the stimulation was verified by pupil size analysis. Behavioral results revealed robust temporal attention benefits on d', reaction time, and the Balanced Integration Score (BIS) across all four TMS conditions, indicating that the benefits of temporal attention were unaffected by occipital TMS. Furthermore, pupil dilation was largest in the both-TMS condition, followed by the T1-TMS and T2-TMS conditions, and smallest in the none-TMS condition, providing physiological verification of the stimulation protocol. Together, these findings reveal the first causal evidence that the early visual cortex is not functionally necessary for endogenous temporal attention.

neuroscience↗

Disentanglement of persistent and dynamic neural substrates of working memory

Competing theories of working memory have alternatively emphasized the importance of persistent and dynamic substrates of this cognitive function. Here, we directly tested these theories by computationally isolating the contributions of persistent and dynamic activity to working memory. We analyzed neuronal population activity recordings in macaques doing match/non-match working memory tasks. We first extracted signatures of persistent and dynamic activity through cue-specific temporal means, temporal principal components, and correlations of activity patterns across task epochs. We then generated synthetic data constrained by these signatures, and decoded cue stimuli from these data, separately from persistent and non-persistent neurons. We found that high decoding performance arose from a nuanced interplay of persistent and dynamic activity. Specifically, we could decode stimuli at empirical or above-chance levels across all tasks only from persistent neurons, but only after constraining correlations of activity patterns across epochs. In this way, we showed distinct roles for persistent and dynamic neuronal activity that help to unify two competing theories of working memory. More broadly, we also advanced computational controlled experiments as a principled framework for adjudicating between competing models of neuronal population activity.

neuroscience↗