The purpose of this article is to introduce the measurements of phase coupling between spikes and rhythmic oscillations of local field potentials (LFPs). Multi-channel in vivo recording techniques allow us to record ensemble neuronal activity and LFPs simultaneously from the same sites in the brain. Neuronal activity is generally characterized by temporal spike sequences, while LFPs contain oscillatory rhythms in different frequency ranges. Phase coupling analysis can reveal the temporal relationships between neuronal firing and LFP rhythms. As the first step, the instantaneous phase of LFP rhythms can be calculated using Hilbert transform, and then for each time-stamped spike occurred during an oscillatory epoch, we marked instantaneous phase of the LFP at that time stamp. Finally, the phase relationships between the neuronal firing and LFP rhythms were determined by examining the distribution of the firing phase. Phase-locked spikes are revealed by the non-random distribution of spike phase. Theta phase precession is a unique phase relationship between neuronal firing and LFPs, which is one of the basic features of hippocampal place cells. Place cells show rhythmic burst firing following theta oscillation within a place field. And phase precession refers to that rhythmic burst firing shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This relation between phase and position can be described by a linear model, and phase precession is commonly quantified with a circular-linear coefficient. Phase coupling analysis helps us to better understand the temporal information coding between neuronal firing and LFPs.
Action Potentials ; Hippocampus ; physiology ; Neurons ; physiology ; Periodicity

Entorhinal Cortex/physiology* ; Hippocampus/physiology* ; Neural Pathways/physiology*

In central nervous system only a limited number of vesicles exist in the presynaptic terminals. The size and fusion modes of the vesicles were particularly important because of their potential impact on neuronal communications. Efficient methods were needed to analyze the recycling kinetics of synaptic vesicle and the size of readily releasable pool (RRP). In this study, fluorescent dyes with different affinity for membranes (FM1-43 with high affinity and FM2-10 with low affinity) were used to stain the functional synaptic vesicles of cultured hippocampal neurons and the kinetics of vesicle recycling was measured. The results showed that the destaining proportion was larger for FM2-10 than that for FM1-43 during the first trial, while it was greater for FM1-43 than FM2-10 during the second and third trials (first round, 93.0%+/-5.9% versus 57.9%+/-3.5% for FM2-10 and FM1-43, respectively, P<0.0001; second round, 1.4%+/-3.8% versus 24.0%+/-2.3%, P<0.0001; third round, 2.3%+/-1.6% versus 8.6%+/-1.5%, P=0.005). The results indicated that rapid endocytosis existed not only in the first round but also occurred when the vesicles were reused. Moreover, Both high-frequency stimuli and hypertonic sucrose stimuli were used to estimate the RRP sizes in the mix cultured hippocampal inhibitory neurons at 13-14 days in vitro (DIV). We found that the RRP size estimated by hypertonic sucrose stimuli [(200+/-23.0) pC] was much larger than that estimated by high-frequency stimuli [(51.1+/-10.5) pC]. One possible reason for the discrepancies in RRP estimates is that in mix cultured conditions, one neuron may receive inputs from several neurons and hypertonic sucrose stimuli will cause RRP of all those neurons release, while using dual patch recording, only the connection between two neurons was analyzed. Thus, to exclude out the impacts of inputs numbers on RRP sizes, it is more reasonable to use high-frequency stimuli to estimate the RRP size in mix cultured neurons.
Cells, Cultured ; Endocytosis ; Hippocampus ; cytology ; Neurons ; physiology ; Synaptic Vesicles ; physiology

Neural oscillations reflect synchronized activities of neuronal ensembles in central nervous system. In the hippocampus, thalamus, neocortex and other brain subregions, neural oscillation can be detected and plays a crucial role in many complicated cognitive processes. Decoupling and damaging of neural oscillation play a key role in the induction of severe cognition deficits in many psychiatric disorders. In this review, we summarize research advances in the underlying mechanisms and physiological functions of neural oscillations. We also discuss the abnormal changes of sharp wave-ripple, gamma oscillation and sleep spindle oscillation in major depressive disorder, schizophrenia and Alzheimer's disease, etc. Finally, the application potential of neural oscillations as clinical diagnosis and treatment targets is evaluated and prospected.
Depressive Disorder, Major ; Hippocampus/physiology* ; Humans ; Neurons ; Sleep/physiology*

To determine the characteristics of spontaneous discharges of hippocampal pyramidal cells (PCs), extracellular neuronal firing in CA1 and CA3 regions of dorsal hippocampus was recorded, the firing modes and interspike interval (ISI) were analyzed with the conventional and nonlinear methods. PCs were discriminated from interneurons using the measurement of action-potential duration and firing rate in this study. There was no significant difference in duration, mean firing frequency, complexity and firing mode between the neurons in CA1 and CA3 regions both in anesthetized and awake animals. The complexity of neurons was higher in awake group than that in anesthetized group, though no difference was found in firing rate. There were differences in the type of pyramidal cells and the coefficient of variance of ISI of neurons. The results obtained from the spontaneous discharges of dorsal hippocampal pyramidal cells reveal some nonlinear and linear aspects in anesthetized and awake states. It seems likely that the combination of conventional and non-linear measurements of the hippocampal pyramidal cells encoding may reflect genuine characteristics of the hippocampal pyramidal cells.
Action Potentials ; physiology ; Animals ; Female ; Guinea Pigs ; Hippocampus ; physiology ; Male ; Microelectrodes ; Neurons ; physiology ; Pyramidal Cells ; physiology

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca²⁺ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca²⁺ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca²⁺ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.
Mice ; Animals ; Primary Visual Cortex ; Extinction, Psychological/physiology* ; Learning/physiology* ; Fear/physiology* ; Hippocampus/physiology*

The hippocampus has been extensively implicated in spatial navigation in rodents and more recently in bats. Numerous studies have revealed that various kinds of spatial information are encoded across hippocampal regions. In contrast, investigations of spatial behavioral correlates in the primate hippocampus are scarce and have been mostly limited to head-restrained subjects during virtual navigation. However, recent advances made in freely-moving primates suggest marked differences in spatial representations from rodents, albeit some similarities. Here, we review empirical studies examining the neural correlates of spatial navigation in the primate (including human) hippocampus at the levels of local field potentials and single units. The lower frequency theta oscillations are often intermittent. Single neuron responses are highly mixed and task-dependent. We also discuss neuronal selectivity in the eye and head coordinates. Finally, we propose that future studies should focus on investigating both intrinsic and extrinsic population activity and examining spatial coding properties in large-scale hippocampal-neocortical networks across tasks.
Animals ; Humans ; Spatial Navigation/physiology* ; Hippocampus/physiology* ; Primates ; Neurons/physiology* ; Theta Rhythm/physiology*

Animals ; Electric Stimulation ; Hippocampus ; physiology ; Male ; Nerve Endings ; physiology ; Rats ; Rats, Sprague-Dawley ; Vagus Nerve ; physiology

Astrocytes are increasingly recognized to play an active role in learning and memory, but whether neural inputs can trigger event-specific astrocytic Ca²⁺ dynamics in real time to participate in working memory remains unclear due to the difficulties in directly monitoring astrocytic Ca²⁺ dynamics in animals performing tasks. Here, using fiber photometry, we showed that population astrocytic Ca²⁺ dynamics in the hippocampus were gated by sensory inputs (centered at the turning point of the T-maze) and modified by the reward delivery during the encoding and retrieval phases. Notably, there was a strong inter-locked and antagonistic relationship between the astrocytic and neuronal Ca²⁺ dynamics with a 3-s phase difference. Furthermore, there was a robust synchronization of astrocytic Ca²⁺ at the population level among the hippocampus, medial prefrontal cortex, and striatum. The inter-locked, bidirectional communication between astrocytes and neurons at the population level may contribute to the modulation of information processing in working memory.
Animals ; Astrocytes ; Hippocampus/physiology* ; Humans ; Memory, Short-Term/physiology* ; Mice ; Neurons/physiology* ; Population Dynamics

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.
Humans ; Hippocampus/physiology* ; Anxiety ; Anxiety Disorders ; Neurotransmitter Agents ; Neuropeptides