Periodic Reporting for period 3 - SleepBalance (Sleep balancing abstraction and forgetting of memory)
Berichtszeitraum: 2023-11-01 bis 2025-04-30
Sleep is known to supports the formation of long-term memory, a function that has been described as an “active systems consolidation” process. However, there is also the long held view that sleep serves to forget unimportant memory. Paradoxically, although this view is supported by evidence of a global synaptic downscaling induced during sleep, there has been little behavioral evidence supporting the idea that sleep can induce forgetting of unimportant information. Against this backdrop, the project examines the central hypothesize that memory processing during sleep is balanced: On the one hand, sleep consolidates memories but, only abstracted, schema-like versions of the originally encoded episodic memories. This consolidation process is, on the other hand, coupled to an active forgetting of episodic detail. I further hypothesised that this twofold function of sleep is most prominently expressed after learning large amounts of information exhausting the limited capacities of memory processing during sleep. It is particularly pronounced during development when due to a lack of pre-existing knowledge, the brain faces conditions of permanent information overload.
The project combines studies in rodents with human studies to test the behavioral predictions of this hypothesis and to characterize the underlying neural mechanisms. It addresses the following specific aims:
1) to provide direct behavioral evidence that with high information load, sleep compared to wakefulness induces forgetting of episodic detail in favour of consolidating abstracted schema-like memory.
2) to clarify how memory abstraction and forgetting are linked to slow wave sleep (SWS) and REM sleep, their characteristic EEG oscillations (i.e. neocortical slow oscillations, thalamic spindles, hippocampal ripples, and EEG theta activity, respectively) underlying forming and pruning of synapses.
3) to demonstrate enhanced sleep-dependent memory abstraction and forgetting during early development.
This project by providing first-time systematic evidence that and how sleep transforms memory to induce forgetting, aims to advance our understanding of sleep’s memory function. It is primarily a basic research project. However, if successful, multiple applications arise not only for the targeted use of sleep in the treatment of various memory-related diseases (including diseases, like addictive behaviors that ground on maladaptive memories that need to be erased). Also, the insights gained in this project can be used for enhancing memory formation as needed in educational and school settings. This is the more relevant as the project has a strong focus on sleep-dependent formation of memory during early development.
The project combines studies in rodents with human studies to test the behavioral predictions of this hypothesis and to characterize the underlying neural mechanisms. It addresses the following specific aims:
1) to provide direct behavioral evidence that with high information load, sleep compared to wakefulness induces forgetting of episodic detail in favour of consolidating abstracted schema-like memory.
2) to clarify how memory abstraction and forgetting are linked to slow wave sleep (SWS) and REM sleep, their characteristic EEG oscillations (i.e. neocortical slow oscillations, thalamic spindles, hippocampal ripples, and EEG theta activity, respectively) underlying forming and pruning of synapses.
3) to demonstrate enhanced sleep-dependent memory abstraction and forgetting during early development.
This project by providing first-time systematic evidence that and how sleep transforms memory to induce forgetting, aims to advance our understanding of sleep’s memory function. It is primarily a basic research project. However, if successful, multiple applications arise not only for the targeted use of sleep in the treatment of various memory-related diseases (including diseases, like addictive behaviors that ground on maladaptive memories that need to be erased). Also, the insights gained in this project can be used for enhancing memory formation as needed in educational and school settings. This is the more relevant as the project has a strong focus on sleep-dependent formation of memory during early development.
Work performed within this project so far have concentrated on aims 1 and 3 as specified above. As to aim 1, we succeeded in providing direct behavioral evidence that sleep favours the consolidation of abstracted, schema-like memory, using a spatial schema-learning task in rats. Notably, schema memory formation in animals sleeping after learning, was only observed with high information load during the learning phase, whereas with low information load episodic memory (for the spatial configurations of individual episodes) prevailed (Harkotte et al. 2022). In a second study regarding aim 1, contrasting sleep and wake-dependent consolidation processes, we showed that unlike wake consolidation, formation of schema memory during sleep originates from contextual hippocampal, i.e. episodic memory representations (Sawangjit et al. 2022). This study can be considered a breakthrough in the field because it demonstrated, for the first time, that in certain conditions consolidation processes during wakefulness are superior to those during sleep.
As to aim 3, we provided first evidence in rats that spatial schema-like memory can be formed already on postnatal day 16 which is distinctly earlier then it was found in other studies, with this preweaning time roughly corresponding to human infancy, < 1 yrs old. This early spatial memory formation is not only sleep-dependent but, essentially linked to activation of the medial prefrontal cortex (mPFC) areas, like the prelimbic region of the mPFC (Shan et al. 2022, Contreras et al. 2023a). We, moreover, provided first evidence suggesting that the mechanisms enabling sleep-dependent formation of abstracted schema-like memory in adults via a hippocampal-neocortical information transfer, show a rather slow, experience-driven maturation (Contreras et al. 2023b). Suggesting that an adult-like memory formation is effective not before childhood, these findings implicate that sleep-dependent memory formation during infancy is achieved through different mechanisms. This conclusion is also supported by findings from parallel studies in human children and infants (Kurz et al. 2023, Bastian et al. 2023).
As to aim 3, we provided first evidence in rats that spatial schema-like memory can be formed already on postnatal day 16 which is distinctly earlier then it was found in other studies, with this preweaning time roughly corresponding to human infancy, < 1 yrs old. This early spatial memory formation is not only sleep-dependent but, essentially linked to activation of the medial prefrontal cortex (mPFC) areas, like the prelimbic region of the mPFC (Shan et al. 2022, Contreras et al. 2023a). We, moreover, provided first evidence suggesting that the mechanisms enabling sleep-dependent formation of abstracted schema-like memory in adults via a hippocampal-neocortical information transfer, show a rather slow, experience-driven maturation (Contreras et al. 2023b). Suggesting that an adult-like memory formation is effective not before childhood, these findings implicate that sleep-dependent memory formation during infancy is achieved through different mechanisms. This conclusion is also supported by findings from parallel studies in human children and infants (Kurz et al. 2023, Bastian et al. 2023).
Two major conclusions can be drawn from the research so far: (i) Contrasting with consolidation occurring in the wake state, sleep consolidation is a systems consolidation process that is based on processing of hippocampal episodic memory representations and leads to the formation of abstracted representations involving neocortical and, in particular, medial prefrontal cortex areas. (ii) During infancy, sleep supports the very rapid formation of schema-like memory in neocortical networks. However, unlike sleep-dependent memory formation in adulthood, sleep-dependent consolidation of schema-like representations in neocortical networks appear to rely to a lesser extent (or not at all) on the transmission of specific reactivated memory information from hippocampus.
We expect for the remaining period to be able to show that the formation of abstracted schema-like memory during sleep relies on synaptic mechanisms activated in neocortical networks in conjunction with slow oscillations and spindles during slow wave sleep. On the other hand, we expect to be able to show that synaptic mechanisms related to forgetting of memory (down-scaling) during sleep, are preferentially established in hippocampal networks in conjunction with ripples during slow wave sleep and in conjunction with EEG theta activity during REM sleep.
We expect for the remaining period to be able to show that the formation of abstracted schema-like memory during sleep relies on synaptic mechanisms activated in neocortical networks in conjunction with slow oscillations and spindles during slow wave sleep. On the other hand, we expect to be able to show that synaptic mechanisms related to forgetting of memory (down-scaling) during sleep, are preferentially established in hippocampal networks in conjunction with ripples during slow wave sleep and in conjunction with EEG theta activity during REM sleep.