Oscillations and hippocampal–prefrontal synchrony

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The hippocampus, a structure required for many types of memory, connects to the medial prefrontal cortex, an area that helps direct neuronal information streams during intentional behaviors. Increasing evidence suggests that oscillations regulate communication between these two regions. Theta rhythms may facilitate hippocampal inputs to the medial prefrontal cortex during mnemonic tasks and may also integrate series of functionally relevant gamma-mediated cell assemblies in the medial prefrontal cortex. During slow-wave sleep, temporal coordination of hippocampal sharp wave-ripples and medial prefrontal cortex spindles may be an important component of the process by which memories become hippocampus-independent. Studies using rodent models indicate that oscillatory phase-locking is disturbed in schizophrenia, emphasizing the need for more studies of oscillatory synchrony in the hippocampal–prefrontal network.

Highlights

► Coherent oscillations are observed across the hippocampus and medial prefrontal cortex (mPFC). ► Hippocampal theta oscillations modulate mPFC during goal-directed behaviors and working memory. ► Bursts of mPFC gamma oscillations, phase-locked to hippocampal theta, may also subserve such tasks. ► Hippocampal sharp waves and mPFC spindles may promote transfer of memories from hippocampus to mPFC. ► Oscillatory phase-locking between hippocampus and mPFC may be disrupted during schizophrenia.

Introduction

The hippocampus is required for several types of memory [1]. It must cooperate with other structures that are involved in learning and memory, and brain rhythms are thought to be important for coordinating these interactions. When large groups of neurons synchronize their electrical activity in a periodic manner, brain rhythms (or oscillations) emerge in local field potential (LFP) recordings. The hippocampus exhibits three main classes of rhythms that are associated with particular behavioral states [2]: theta, gamma, and sharp wave-ripples. Theta rhythms (∼5–10 Hz) occur during active behaviors as well as REM sleep [3] and are believed to be important for learning and memory [4]. Gamma oscillations are faster waves (∼25–140 Hz) that occur during many behaviors but are largest when theta rhythms are present [5]. Ripples are very fast oscillations (∼150–300 Hz) that are superimposed on slow and irregularly occurring ‘sharp waves’ (∼1–10 Hz). Sharp-wave ripple complexes emerge during slow-wave sleep and periods of inactivity [6]. Each of these three classes of rhythms is believed to play a unique role in coordinating interactions between the hippocampus and the systems with which it communicates.

One region that interacts with the hippocampus is the medial prefrontal cortex (mPFC). The mPFC is important for working memory, as well as executive functions including decision-making, goal-oriented behaviors, and attentional selection of task-relevant information [7]. The mPFC receives direct projections from ventral CA1 and subiculum subfields of the hippocampus [8, 9], and these synapses are plastic [10]. The hippocampus is believed to activate mPFC during behaviors in which functions of mPFC are required. For example, the hippocampus may encode a memory of a particular circumstance that is associated with a particular goal-directed behavior. When this circumstance arises later, the hippocampus may retrieve its memory of this circumstance and communicate to the prefrontal cortex so that behavior can be adjusted to achieve the desired goal.

I review recent studies that support the hypothesis that rhythms facilitate functional interactions between the hippocampus and mPFC during behaviors requiring both regions. Owing to the complexities related to defining homologous areas of the prefrontal cortex across species [9, 11], this review focuses on rodent studies. However, coherent oscillations in the hippocampus and mPFC are believed to mediate memory operations in humans (e.g. [12, 13]) and other species also.

Section snippets

Theta interactions between mPFC and hippocampus

Theta rhythms coordinate the activity of neurons on a relatively slow time scale. Slow oscillations are capable of coordinating activity across widespread networks of neurons because neurons in areas that are separated by long conduction delays can still be activated within the same oscillatory cycle [14]. Monosynaptic delays between the hippocampus and mPFC have been reported to be ∼15 ms [15]. Thus, the ∼150 ms period of a theta cycle would certainly be capable of coordinating direct

Gamma interactions between mPFC and hippocampus

Gamma oscillations co-occur with theta rhythms in the hippocampus. However, few studies have addressed the question of whether synchronous gamma activity between the hippocampus and mPFC affects mnemonic processing. Although more work is needed, a number of recent results have provided clues about how gamma may coordinate interactions between the regions on a fast time scale.

In the hippocampus, the amplitude of gamma oscillations is modulated by theta phase [5]. This may imply that

Oscillatory interactions between mPFC and hippocampus during slow-wave sleep

One theory of memory consolidation posits that certain memories initially depend on the hippocampus but then gradually are transferred to the neocortex [37], possibly during slow-wave sleep. In slow-wave sleep, hippocampal neurons that were co-active during wakefulness reactivate together during sharp wave-ripples [38]. Similarly, mPFC neurons that fired together during waking reactivate together during subsequent slow-wave sleep [39]. Reactivation of mPFC neurons may be coordinated by

Disrupted hippocampal–mPFC synchrony in rodent models of schizophrenia

The prefrontal cortex is one of the main brain regions implicated in the neuropathology of schizophrenia [45]. Moreover, disturbances in functional connectivity between the hippocampus and prefrontal cortex have been reported in schizophrenic patients [46, 47]. In light of this, two recent studies have used rodent models of schizophrenia to investigate how oscillatory phase-locking between the hippocampus and mPFC is affected by the disease.

The first study investigated mPFC–hippocampal

Conclusions

The above-discussed studies have advanced our knowledge of how oscillations affect functions that are handled jointly by the mPFC and hippocampus. Coherent theta oscillations coordinate interactions between the hippocampus and mPFC during complex cognitive operations such as working memory. Hippocampal theta modulation of mPFC gamma oscillations may also play an important role in coordinating interactions between the regions. Reactivation of mPFC neurons by hippocampal sharp wave-ripples may

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

I thank Michael Drew and Michael Mauk for helpful comments. Funding was provided by University of Texas start-up funds and grant P30 MH089900 from NIMH.

References (51)

  • C.M. Wierzynski et al.

    State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep

    Neuron

    (2009)
  • M.P. Witter et al.

    Hippocampal formation

  • D.A. Lewis et al.

    Cortical inhibitory neurons and schizophrenia

    Nat Rev Neurosci

    (2005)
  • T.U. Woo et al.

    Gamma oscillation deficits and the onset and early progression of schizophrenia

    Harv Rev Psychiatry

    (2010)
  • L.R. Squire et al.

    The medial temporal lobe

    Annu Rev Neurosci

    (2004)
  • G. Buzsaki

    Theta rhythm of navigation: link between path integration and landmark navigation, episodic and semantic memory

    Hippocampus

    (2005)
  • A. Bragin et al.

    Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat

    J Neurosci

    (1995)
  • E.K. Miller et al.

    An integrative theory of prefrontal cortex function

    Annu Rev Neurosci

    (2001)
  • T.M. Jay et al.

    Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin

    J Comp Neurol

    (1991)
  • W.B. Hoover et al.

    Anatomical analysis of afferent projections to the medial prefrontal cortex in the rat

    Brain Struct Funct

    (2007)
  • K.L. Anderson et al.

    Theta oscillations mediate interaction between prefrontal cortex and medial temporal lobe in human memory

    Cereb Cortex

    (2010)
  • P.B. Sederberg et al.

    Gamma oscillations distinguish true from false memories

    Psychol Sci

    (2007)
  • G. Buzsaki et al.

    Neuronal oscillations in cortical networks

    Science

    (2004)
  • T.M. Jay et al.

    Excitatory amino acid pathway from the hippocampus to the prefrontal cortex. Contribution of AMPA receptors in hippocampo-prefrontal cortex transmission

    Eur J Neurosci

    (1992)
  • M.W. Jones et al.

    Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task

    PLoS Biol

    (2005)
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