Science, Vol 377, Issue 6603, pp. 262-263, 15 July 2022

Cellular Switchboard in Memory Circuits

Michael T. Craig, et.al.

School of Psychology and Neuroscience, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.

Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, UK.

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The hippocampus is a brain region that is associated with memory. However, the hippocampus does not function alone, but rather operates within a wider network of brain regions (the extended memory network) including, among other areas, the prefrontal and entorhinal cortices and midline thalamic nuclei, such as nucleus reuniens (NRe). Communication between these brain regions is important for many aspects of memory acquisition and consolidation, as well as for spatial navigation and decision-making. There are multiple routes through which information can flow through the extended memory network, with direct and indirect pathways converging on the hippocampus.

Communication between neurons is thought to be enabled by neuronal oscillations—waves of rhythmic electrical activity that facilitate neural dialogue by creating temporal windows in which neuronal firing can be synchronized. Neuronal oscillations are grouped into different frequency bands, with each band associated with specific cognitive processes. For example, theta oscillations occur at ∼5 to 12 Hz and are associated with spatial navigation, whereas gamma oscillations occur between ∼30 and 140 Hz and are associated with memory or high cognitive load.    Gamma oscillations, often occurring alongside theta oscillations, can be further parsed into distinct subbands driven by different cellular mechanisms. This can be observed in the CA1 region of the hippocampus, where different types of gamma oscillation are found—specifically, a slow gamma oscillation (gamma_S; ∼40 Hz) driven by input from neighboring CA3 and a faster midfrequency gamma oscillation (gamma_M; ∼75 Hz) driven by input from the entorhinal cortex. Gamma_M may be involved in the encoding of memory, whereas gamma_S is likely to be important for memory retrieval.

Pyramidal neurons form the main computational unit of the hippocampus, with those in CA1 integrating inputs from multiple sources and sending signals to the subiculum and beyond through the generation of action potentials (also called spiking). Inputs to CA1 from CA3 arrive in stratum radiatum of the hippocampus, whereas those from the entorhinal cortex terminate in stratum lacunosum-moleculare of the hippocampus, providing an anatomical segregation of these different information streams. There is also a functional segregation of CA3- and entorhinal-driven gamma oscillations: These different types of oscillation occur at different phases of the CA1 theta oscillation, potentially presenting a circuit-level mechanism that prevents the processes driven by different information streams (e.g., memory encoding versus retrieval) from interfering with each other. Whether the inputs to an individual pyramidal cell in CA1 can be actively switched between these different information streams has been unknown.

Within the hippocampus, inhibitory interneurons make up a diverse family of neurons, using (GABA) as their neurotransmitter, with multiple subtypes providing exquisite temporal control over the spiking of excitatory pyramidal cells and other inhibitory interneurons.    Neuronal oscillations are typically generated through a precisely coordinated balance between excitation and inhibition. Neurogliaform cells are an abundant class of inhibitory interneurons that reside in and project dense axonal arbors throughout stratum lacunosum-moleculare of the hippocampus. They are therefore well placed to inhibit the distal apical dendrites of CA1 pyramidal cells, but understanding their role in hippocampal information processing has remained elusive.

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