A central function of the brain is to create and retain internal representations of the world that could eventually guide behaviour. The term memory refers exactly to this “retention”. Traditionally, three major processes are thought to be involved in memory: encoding, storage, and retrieval. The first process refers to the ability of brains to transform sensory-motor information into widespread neural representations, involving different sensory, associational and modulatory areas and structures of the brain. Once the encoding of information is completed, the state of widespread neural patterns emerging through changes in synaptic connections can be stored, and later potentially retrieved. Memories can be brief and limited or of a seemingly unlimited capacity, dubbed as short-term and long-term memories respectively.  

Long-term memory-formations range from elementary and non-associative types of memory including habituation and sensitization, to complex forms of retention, such as the episodic and semantic memory.  The former stores what, where and when type of information, while the latter refers to the knowledge of facts, events, ideas, and concepts, covering a vast terrain, including information about historical and scientific facts, meaning of words, or even of complex sentences, such as mathematical equations. Episodic and Semantic memories are often grouped together under the term Declarative Memory, in parallel to so-called Procedural Memory that is thought to underlie our ability to develop long-term skills, such as talking, walking, riding a bike, or playing a musical instrument.  Declarative memory involves neuronal assemblies including telencephalon and limbic system, e.g. hippocampus, amygdala and septal nuclei, while the procedural memory involves neuronal assemblages of primary sensory and motor areas, association cortices, and structures, such as the striatum and cerebellum. 

Beyond the differences in neural infrastructure, the consolidation of the two aforementioned memories occurs during different sleep states, such as the REM (Rapid Eye-Movement) and non-REM (NREM) sleep. The striking, distinct characteristics of these sleep states have long been studied by using polygraphic recordings, including electromyograms, electrooculograms, and electrophysiological recordings.  REM starts approximately 90 minutes after we fall asleep, lasting about 10 minutes, while its duration in the final sleep-phase gradually reaches an entire hour. REM epochs are characterized by characteristic eye movements, increased heart and breathing rate, and dreaming. NREM epochs, instead, are associated with deeper sleep-stages, the deepest of which, known as slow-wave sleep due to the cortical slow up-down oscillations, has been associated with the consolidation of declarative memory. REM and NREM have entirely different neurochemical niveau and are marked by different intrinsic neural events, such as the Pontine-Geniculate-Occipital waves (PGOw) emerging in the pontine region, and the Sharp-Wave Ripples (SWR) and Theta-bouts (i.e. brief oscillations in the 2-15Hz), appearing in the Hippocampus. Hippocampus has long been known to play a major role in encoding and consolidating long-term memories, undergoing plastic changes during sleep, and SWR were considered to be the manifestation of so-called system-consolidation following the intensive interactions between hippocampus and cortex. Yet, system-consolidation alone would be unable to create enduring memories, as the cortical changes induced by hippocampal-cortical interactions would require precise homeostatic control by subcortical neuromodulatory structures, promoting long term potentiation. Pontine cholinergic activity, potentially mediated through the PGOw, could be one good example. But would then SWR events coincide with some kind of pontine activity? 

In the study, published in the recent issue of Nature, the group of Logothetis used multi-structure recordings in macaque monkeys, and demonstrated for the first time that the brainstem indeed transiently modulates the hippocampal network-events through the PGOw. Two physiologically distinct types of PGOw appear to occur sequentially, selectively influencing high-frequency ripples and low-frequency theta events, respectively. The two PGOw types are associated with opposite hippocampal spike-field coupling, prompting periods of high neural synchrony of neural populations during periods of ripple and theta instances. The physiology results were prompted and subsequently also supported by neural-event triggered functional MRI, demonstrating the value of multidisciplinary methods in systems neuroscience. 

This utterly surprising coupling between PGOw and ripples supports the notion that a global coordination mechanism of hippocampal sleep dynamics by cholinergic pontine transients may promote systems and synaptic memory consolidation as well as synaptic homeostasis. 

Professor Logothetis is the incoming Co-Director of International Center of Primate Brain Research, Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences.