Oscillations and hippocampal–prefrontal synchrony
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.
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