Dissociated theta phase synchronization in amygdalo- hippocampal circuits during various stages of fear memory.
ABSTRACT The amygdala and the hippocampus are critically involved in the formation and retention of fear memories. However, their precise contribution to, and their interplay during, fear memory formation are not fully understood. In the present study we investigated network activities in the amygdalo-hippocampal system of freely behaving mice at different stages of fear memory consolidation and retention. Our data show enhanced theta phase synchronization in this pathway during the retrieval of fear memory at long-term (24 h post-training), but not short-term (2 min, 30 min and 2 h post-training) stages, following both contextual and auditory cued conditioning. However, retrieval of remotely conditioned fear (30 days post-training) failed to induce an increase in synchronization despite there still being memory retention. Thus, our data indicate that the amygdalo-hippocampal interaction reflects a dynamic interaction of ensemble activities related to various stages of fear memory consolidation and/or retention, and support the notion that recent and remote memories are organized through different network principles.
- SourceAvailable from: Lucien T. Thompson[show abstract] [hide abstract]
ABSTRACT: It is well established that physical changes to an environment result in plasticity of hippocampal place cell activity, while in the absence of changes, place fields are remarkably stable. Manipulations of a rat's perception of the environment without physically changing the environment also result in plasticity of place cell firing. Here, we tested the hypothesis that a rat's perception of an environment could be changed by introducing an auditory fear-conditioned stimulus (CS) to a previously neutral environment, inducing plasticity of hippocampal place fields. First, stable place fields were isolated for rats exploring a radial-arm maze in one environment, and then the rats were fear-conditioned to an auditory CS in a completely separate environment. Later, the CS was specifically paired once with a location in the previously neutral radial-arm maze, either within the given neuron's place field (in-field) or an area outside of the place field (out-of-field). A single, paired presentation of the CS with a location in-field for a specific place cell disrupted the stability of that neuron's place field, whereas pairing the CS with a location out-of-field did not affect place field stability. We further showed that this place field disruption for a CS presented in-field was mediated by inputs from the basolateral amygdala (BLA). Temporarily inactivating the BLA immediately post-CS re-exposure attenuated the CS-induced place field destabilization. Our results show neuron-specific conditional plasticity for actively firing hippocampal place cells, and that the BLA mediates this plasticity when an emotionally arousing or fear-related CS is used.Brain Research 08/2013; 1525:16-25. · 2.88 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Theta oscillations are considered crucial mechanisms in neuronal communication across brain areas, required for consolidation and retrieval of fear memories. One form of inhibitory learning allowing adaptive control of fear memory is extinction, a deficit of which leads to maladaptive fear expression potentially leading to anxiety disorders. Behavioral responses after extinction training are thought to reflect a balance of recall from extinction memory and initial fear memory traces. Therefore, we hypothesized that the initial fear memory circuits impact behavioral fear after extinction, and more specifically, that the dynamics of theta synchrony in these pathways signal the individual fear response. Simultaneous multi-channel local field and unit recordings were obtained from the infralimbic prefrontal cortex, the hippocampal CA1 and the lateral amygdala in mice. Data revealed that the pattern of theta coherence and directionality within and across regions correlated with individual behavioral responses. Upon conditioned freezing, units were phase-locked to synchronized theta oscillations in these pathways, characterizing states of fear memory retrieval. When the conditioned stimulus evoked no fear during extinction recall, theta interactions were directional with prefrontal cortical spike firing leading hippocampal and amygdalar theta oscillations. These results indicate that the directional dynamics of theta-entrained activity across these areas guide changes in appraisal of threatening stimuli during fear memory and extinction retrieval. Given that exposure therapy involves procedures and pathways similar to those during extinction of conditioned fear, one therapeutical extension might be useful that imposes artificial theta activity to prefrontal cortical-amygdalo-hippocampal pathways that mimics the directionality signaling successful extinction recall.PLoS ONE 01/2013; 8(10):e77707. · 3.73 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Methods of cell biology and electrophysiology using dissociated primary cultured neurons allow in vitro study of molecular functions; however, analysis of intact neuronal circuitry is often preferable. To investigate exogenous genes, viral vectors are most commonly injected using a pipette that is inserted from the top of the cortex. Although there are few reports that describe the success rate of injection in detail, it is sometimes difficult to locate the pipette tip accurately within the CA1 pyramidal cell layer because the pyramidal layer is only 0.1 mm thick. In the present study, we have developed a system to inject viral vectors accurately into the mouse hippocampal CA1 pyramidal cell layer using a stereotaxic injection system with simultaneous electrophysiological monitoring of theta oscillation. The pipette tip was positioned reliably based on integrated values of the theta oscillation in the hippocampal CA1 pyramidal cell layer. This approach allows accurate injection of solutions and provides an efficient method of gene transfer using viral vectors into the hippocampus, which can be a useful tool for studies involving the molecular mechanisms of neuronal functions.PLoS ONE 01/2013; 8(12):e83129. · 3.73 Impact Factor