Sets of spikes emitted sequentially across neurons constitute fundamental pulse packets in neural information processing, including offline memory replay during hippocampal sharp-wave ripples (SWRs). The relative timing of neuronal spikes is fine-tuned in each spike sequence but can vary between different sequences. However, the microcircuitry mechanism that enables such flexible spike sequencing remains unexplored. We recorded the membrane potentials of multiple hippocampal CA1 pyramidal cells in mice and found that the neurons were transiently hyperpolarized prior to SWRs. The pre-SWR hyperpolarizations were spatiotemporally heterogeneous, and larger hyperpolarizations were associated with later spikes during SWRs. Intracellular blockade of Cl−-mediated inhibition reduced pre-SWR hyperpolarizations and advanced spike times. Single-unit recordings also revealed that the pre-SWR firing rates of inhibitory interneurons predicted the SWR-relevant spike times of pyramidal cells. Thus, pre-SWR inhibitory activity determines the sequential spike times of pyramidal cells and diversifies the repertoire of sequence patterns.

Perineuronal nets (PNNs) are distributed primarily around inhibitory interneurons in the hippocampus, such as parvalbumin-positive interneurons. PNNs are also present around excitatory neurons in some brain regions and prevent plasticity in these neurons. A recent study demonstrated that PNNs also exist around mouse hippocampal pyramidal cells, which are the principle type of excitatory neurons, in the CA2 subregion and modulate the excitability and plasticity of these neurons. However, the development of PNNs in the CA2 region during postnatal maturation was not fully investigated. This study found that a main component of PNNs, aggrecan, existed in the pyramidal cell layer of the putative CA2 subarea prior to the appearance of the CA2 region, which was defined by the CA2 marker protein regulator of G protein signaling 14 (RGS14). We also found that aggrecan immunoreactivity was more evident in the anterior sections of the CA2 area than the posterior sections, which suggests that the function of CA2 PNNs varies along the anterior-posterior axis.

Brain functions are fundamental for the survival of organisms, and they are supported by neural circuits consisting of a variety of neurons. To investigate the function of neurons at the single-cell level, researchers often use whole-cell patch-clamp recording techniques. These techniques enable us to record membrane potentials (including action potentials) of individual neurons of not only anesthetized but also actively behaving animals. This whole-cell recording method enables us to reveal how neuronal activities support brain function at the single-cell level. In this review, we introduce previous studies using in vivo patch-clamp recording techniques and recent findings primarily regarding neuronal activities in the hippocampus for behavioral function. We further discuss how we can bridge the gap between electrophysiology and biochemistry.

Normal respiratory and circulatory functions are crucial for survival. However, conventional methods of monitoring respiration, some of which use sensors inserted into the nasal cavity, may interfere with naïve respiratory rates. In this study, we conducted a single-point measurement of electrocardiograms (ECGs) from the pectoral muscles of anesthetized and waking mice and found low-frequency oscillations in the ECG baseline. Using the fast Fourier transform of simultaneously recorded respiratory signals, we demonstrated that the low-frequency oscillations corresponded to respiratory rhythms. Moreover, the baseline oscillations changed in parallel with the respiratory rhythm when the latter was altered by pharmacological manipulation. We also demonstrated that this method could be combined with in vivo whole-cell patch-clamp recordings from the hippocampus. Thus, we developed a non-invasive form of respirometry in mice. Our recording method using a simple derivation algorithm is applicable to a variety of physiological and pharmacological experiments, providing an experimental platform in studying the mechanisms underlying the interaction of the central nervous system and the peripheral functions.

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