Input source and strength influences overall firing phase of model hippocampal CA1 pyramidal cells during theta: relevance to REM sleep reactivation and memory consolidation

In simulation studies using a realistic model CA1 pyramidal cell, we accounted for the shift in mean firing phase from theta cycle peaks to theta cycle troughs during rapid-eye movement (REM) sleep reactivation of hippocampal CA1 place cells over several days of growing familiarization with an environment (Brain Res 855:176-180). Changes in the theta drive phase and amplitude between proximal and distal dendritic regions of the cell modulated the theta phase of firing when stimuli were presented at proximal and distal dendritic locations. Stimuli at proximal dendritic sites (proximal to 100 microm from the soma) invoked firing with a significant phase preference at the depolarizing theta peaks, while distal stimuli (>290 microm from the soma) invoked firing at hyperpolarizing theta troughs. The input location-related phase preference depended on active dendritic conductances, a sufficient electrotonic separation between input sites and theta-induced subthreshold membrane potential oscillations in the cell. The simulation results predict that the shift in mean theta phase during REM sleep cellular reactivation could occur through potentiation of distal dendritic (temporo-ammonic) synapses and depotentiation of proximal dendritic (Schaffer collateral) synapses over the course of familiarization.     

Phase relations of rhythmic neuronal firing in the supramammillary nucleus and mammillary body to the hippocampal theta activity in urethane anesthetized rats

Structures in the caudal diencephalon including the posterior hypothalamic nucleus, the supramammillary nucleus (SUM) and the nuclei of the mammillary body (MB) occupy a strategic position in the crossroads of ascending and descending traffic between the brainstem and the limbic forebrain (septum/hippocampus). In this study we analyzed the phase relations of rhythmically discharging SUM/MB cells to hippocampal theta rhythm in urethane anesthetized rats with a dual aim of separating different functional types of SUM and MB neurons and characterizing their coupling to septohippocampal theta oscillators. We found that rhythmically firing neurons in the SUM/MB represent a functionally heterogeneous population of cells that are coupled with forebrain theta oscillators at different preferred phases. Based on their phase relations to hippocampal theta four groups of rhythmic SUM/MB cells were identified. Neurons of the first and second groups fired out-of-phase relative to each other and synchronously with the positive (8° ± 7) or negative peaks (−177° ± 7) of theta field activity in the hippocampus, recorded above the CA1 pyramidal layer. Cells of the other two groups, also forming out-of-phase counterparts, fired on the rising (97° ± 9) or falling segments (−97° ± 6) of CA1 theta waves. The peaks in the phase distribution histogram were well separated, and the empty zones between them were wider (40–70°) than those comprising the phase data for different groups. The variations of phase values for individual neurons, when tested during several theta epochs, did not exceed the range of a single group. Theta field potentials were also recorded in the SUM/MB and were advanced by one quarter of the cycle (79° ± 9, range 56–99°) relative to CA1 theta oscillations. The present results indicate that, similar to other theta-generating structures, rhythmically firing neurons can be classified on the basis of their phase relations in the SUM/MB as well. Different classes of SUM/MB neurons might play different roles in generating and/or transmitting theta rhythmic activity of the limbic system. Hippocampus 7:204–214, 1997. © 1997 Wiley-Liss, Inc.     

An olfactory input to the hippocampus of the cat: Field potential analysis

Hippocampal responses to electrical stimulation of the prepyriform cortex in the cat were studied both in acute experiments under halothane anesthesia and in awake cats with chronically indwelling electrodes. Analysis of field potentials and unit activity indicated the extent to which different hippocampal subareas were activated, the laminar level at which the synaptic action took place and the dynamics of the evoked responses. It was found that: (1) the main generator of evoked responses in the hippocampus upon prepyriform cortex stimulation is localized in the fascia dentata and CA3 (CA1 pyramidal cells, and probably also subiculum cells, are activated but in a lesser degree); (2) the initial synaptic activity takes place at the most distal part of the dendrites of fascia dentata granule cells and CA3 pyramidal cells; and (3) this synaptic activity corresponds to an EPSP that leads to a transient increase in the firing rate of the hippocampal units, which is often followed by a long-lasting decrease in firing rate.We conclude that the pathway from the prepyriform cortex via lateral entorhinal cortex to hippocampal neurons may enable olfactory inputs to effectively excite hippocampal neurons.     

Anatomical correlates of rhythmical slow wave activity (theta) in the hippocampal formation of the cat

The topography of spontaneous and hypothalamically induced hippocampal rhythmical slow wave activity )theta) was studied acutely in cats anesthetized with urethane. Tracking and depth profile analysis using microelectrodes showed two amplitude maxima of theta activity approximately 180° out of phase separated by a null zone. One amplitude peak was located in stratum oriens of CA1 (maximum amplitude 1.2 mV) and the other peak in stratum moleculare of the fascia dentata (maximum amplitude 1.9 mV). The null zone was localized to stratum radiatum, just ventral to the CA1 pyramidal cells. The two ‘generator’ hypothesis of theta activity was discussed in relation to similar findings for other species. Pharmacological results were interpreted as supporting the view that there is an ascending cholinergic input mediating theta in the urethanized cat.     

Environmental novelty elicits a later theta phase of firing in CA1 but not subiculum

The mechanism supporting the role of the hippocampal formation in novelty detection remains controversial. A comparator function has been variously ascribed to CA1 or subiculum, whereas the theta rhythm has been suggested to separate neural firing into encoding and retrieval phases. We investigated theta phase of firing in principal cells in subiculum and CA1 as rats foraged in familiar and novel environments. We found that the preferred theta phase of firing in CA1, but not subiculum, was shifted to a later phase of the theta cycle during environmental novelty. Furthermore, the amount of phase shift elicited by environmental change correlated with the extent of place cell remapping in CA1. Our results support a relationship between theta phase and novelty‐induced plasticity in CA1. © 2009 Wiley‐Liss, Inc.     

Spatial selectivity of unit activity in the hippocampal granular layer

Single neuron activity was recorded in the granular layer of the fascia dentata in freely moving rats, while the animals performed a spatial “working” memory task on an eight-arm maze. Using recording methods that facilitate detection of units with low discharge rates, it was found that the majority (88%) of cells in this layer have mean rates below 0.5 Hz, with a minimum of 0.01 Hz or less. The remaining recorded cells exhibited characteristics typical of the theta interneurons found throughout the hippocampus. Based on several criteria including relative proportion and the relation of their evoked discharges to the population spike elicited by perforant path stimulation, it was concluded that the low-rate cells correspond to granule cells. Granule cells exhibited clear spatially and directionally selective discharge that was at least as selective as that of a sample of CA3 pyramidal cells recorded under the same conditions. Granule cells had significantly smaller place fields than pyramidal cells, and tended to have more discontiguous subfields. There was no spatial correlation among simultaneously recorded adjacent granule cells. Granule cells also exhibited burst discharges reminiscent of complex spikes from pyramidal cells while the animals sat quietly; however, the spike duration of granule cells was significantly shorter than CA3 pyramidal cell spike durations. Under conditions of environmental stability, granule cell place fields were stable for at least several days. Following occasional maze rotations relative to the (somewhat impoverished) visual stimuli of the recording room, granule cell place fields were maintained relative to the distal spatial cues; however, frequent rotations of the maze sometimes resulted in a shift in the reference frame to the maze itself. These observations indicate that granule cells of the fascia dentata provide their CA3 targets with a high degree of spatial information, in the form of a sparsely coded, distributed representation.     

Origin of the synchronized network activity in the rabbit developing hippocampus

Rhythmic spontaneous bursting is a fundamental hallmark of the immature hippocampal activity recorded in vitro. These bursts or giant depolarizing potentials (GDPs) are GABA- and glutamatergic-driven events. The mechanisms of GDPs generation are still controversial, since although a hilar origin has been suggested, GDPs were also recorded from isolated CA3 area. Here, we have investigated the origin of GDPs in hippocampal slices from newborn rabbits. Simultaneous intracellular recordings were performed in CA3, CA1 and the fascia dentata. We found a high degree of correlation between the spontaneous GDPs present in CA3 and CA1 regions. Cross-correlation analysis demonstrated that CA3 firing precedes CA1 by about 192 ms, although a significant population of discharges was recorded first in CA1 (20%). Granule cells (GCs) in the fascia dentata also showed GDPs. The frequency of these events (1.46 ± 1.25 GDPs/min, n = 7) is significantly lower when compared with that from CA3 (3.13 ± 1.43 GDPs/min, n = 10) or CA1 (2.94 ± 1.36 GDPs/min, n = 17). Dual recordings from CA3 and fascia dentata cells showed synchronous bursts in both regions with no prevalent preceding area. By recording from isolated areas we found that CA1, CA3 and the fascia dentata can produce GDPs, suggesting that they emerge as a property of local circuits present throughout the hippocampus.     

Effects of atropine on hippocampal theta cells and complex-spike cells

The medial septal nuclei are essential for the naturally occurring hippocampal theta rhythm. Evidence that the rhythmic activity of the septum is carried via cholinergic afferents to the hippocampus has been: (a) the existence of a cholinergic septo-hippocampal projection, and (b) the sensitivity of one type of theta rhythm to antimuscarinic agents or cholinergic depletion. The muscarinic action of acetylcholine on pyramidal cells, however, is too slow to carry even a 4 Hz signal. Recent in vitro studies have confirmed a fast excitatory response by some hippocampal interneurons to muscarinic agonists. In urethane anesthetized rats, iontophoretic application of atropine to 17 hippocampal theta cells (presumed interneurons) during the theta rhythm, reduced their firing rates to an average of 24% of control rates. The effect of iontophoretic atropine application to 4 CA1 complex-spike cells (presumed pyramidal cells) was a selective elimination of their bursting activity with no significant effect on overall firing rate. The data suggest that: (1) interneuronal firing, during the hippocampal theta rhythm, is dominated by an excitatory cholinergic input and not by excitatory collaterals of pyramidal cells; and (2) somatic burst firing by CA1 pyramidal cells requires the presence of acetylcholine.     

Disrupted‐in‐schizophrenia 1 overexpression disrupts hippocampal coding and oscillatory synchronization

Aberrant proteostasis of protein aggregation may lead to behavior disorders including chronic mental illnesses (CMI). Furthermore, the neuronal activity alterations that underlie CMI are not well understood. We recorded the local field potential and single‐unit activity of the hippocampal CA1 region in vivo in rats transgenically overexpressing the Disrupted‐in‐Schizophrenia 1 (DISC1) gene (tgDISC1), modeling sporadic CMI. These tgDISC1 rats have previously been shown to exhibit DISC1 protein aggregation, disturbances in the dopaminergic system and attention‐related deficits. Recordings were performed during exploration of familiar and novel open field environments and during sleep, allowing investigation of neuronal abnormalities in unconstrained behavior. Compared to controls, tgDISC1 place cells exhibited smaller place fields and decreased speed‐modulation of their firing rates, demonstrating altered spatial coding and deficits in encoding location‐independent sensory inputs. Oscillation analyses showed that tgDISC1 pyramidal neurons had higher theta phase locking strength during novelty, limiting their phase coding ability. However, their mean theta phases were more variable at the population level, reducing oscillatory network synchronization. Finally, tgDISC1 pyramidal neurons showed a lack of novelty‐induced shift in their preferred theta and gamma firing phases, indicating deficits in coding of novel environments with oscillatory firing. By combining single cell and neuronal population analyses, we link DISC1 protein pathology with abnormal hippocampal neural coding and network synchrony, and thereby gain a more comprehensive understanding of CMI mechanisms.     

Population dynamics and theta rhythm phase precession of hippocampal place cell firing: A spiking neuron model

O'Keefe and Recce ([1993] Hippocampus 68:317–330) have observed that the spatially selective firing of pyramidal cells in the CA1 field of the rat hippocampus tends to advance to earlier phases of the electroencephalogram theta rhythm as a rat passes through the place field of a cell. We present here a neural network model based on integrate-and-fire neurons that accounts for this effect. In this model, place selectivity in the hippocampus is a consequence of synaptic interactions between pyramidal neurons together with weakly selective external input. The phase shift of neuronal spiking arises in the model as a result of asymmetric spread of activation through the network, caused by asymmetry in the synaptic interactions. Several experimentally observed properties of the phase shift effect follow naturally from the model, including 1) the observation that the first spikes a cell fires appear near the theta phase corresponding to minimal population activity, 2) the overall advance is less than 360°, and 3) the location of the rat within the place field of the cell is the primary correlate of the firing phase, not the time the rat has been in the field. The model makes several predictions concerning the emergence of place fields during the earliest stages of exploration in a novel environment. It also suggests new experiments that could provide further constraints on a possible explanation of the phase precession effect. © 1996 Wiley-Liss, Inc.     

Firing rate and theta-phase coding by hippocampal pyramidal neurons during 'space clamping'

In the hippocampus, spatial representation of the environment has been suggested to be coded by either the firing rate of pyramidal cell assemblies or the relative timing of the action potentials during the theta EEG cycle. Here, we used a behavioural 'space clamp' method, which involved the confinement of the actively running animal in a defined position in space (running wheel) to examine how 'spatial' and other inputs affect firing rate and timing of hippocampal CA1 pyramidal cells and interneurons. Nineteen per cent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel in a given direction ('wheel' cells). Spatial rotation of the apparatus showed that selective discharge of pyramidal cells in the wheel was under the combined influence of distal and apparatus cues. During steady running, both discharge rate and theta phase were constant. Rotation of the wheel apparatus resulted in a shift of both firing rate and preferred theta phase. The discharge frequency of 'wheel' cells increased threefold (on average) with increasing running velocity. In contrast, change in running speed had relatively little effect on the theta phase-related discharge of 'wheel' cells. Our findings indicate that mechanisms that regulate rate and phase of spikes are overlapping but not necessarily identical.     

Activity dynamics and behavioral correlates of CA3 and CA1 hippocampal pyramidal neurons

The CA3 and CA1 pyramidal neurons are the major principal cell types of the hippocampus proper. The strongly recurrent collateral system of CA3 cells and the largely parallel‐organized CA1 neurons suggest that these regions perform distinct computations. However, a comprehensive comparison between CA1 and CA3 pyramidal cells in terms of firing properties, network dynamics, and behavioral correlations is sparse in the intact animal. We performed large‐scale recordings in the dorsal hippocampus of rats to quantify the similarities and differences between CA1 (n > 3,600) and CA3 (n > 2,200) pyramidal cells during sleep and exploration in multiple environments. CA1 and CA3 neurons differed significantly in firing rates, spike burst propensity, spike entrainment by the theta rhythm, and other aspects of spiking dynamics in a brain state‐dependent manner. A smaller proportion of CA3 than CA1 cells displayed prominent place fields, but place fields of CA3 neurons were more compact, more stable, and carried more spatial information per spike than those of CA1 pyramidal cells. Several other features of the two cell types were specific to the testing environment. CA3 neurons showed less pronounced phase precession and a weaker position versus spike‐phase relationship than CA1 cells. Our findings suggest that these distinct activity dynamics of CA1 and CA3 pyramidal cells support their distinct computational roles. © 2012 Wiley Periodicals, Inc.     

GABAergic contributions to gating,timing, and phase precession of hippocampal neuronal activity during theta oscillations

Successful spatial exploration requires gating, storage, and retrieval of spatial memories in the correct order. The hippocampus is known to play an important role in the temporal organization of spatial information. Temporally ordered spatial memories are encoded and retrieved by the firing rate and phase of hippocampal pyramidal cells and inhibitory interneurons with respect to ongoing network theta oscillations paced by intra‐ and extrahippocampal areas. Much is known about the anatomical, physiological, and molecular characteristics as well as the connectivity and synaptic properties of various cell types in the hippocampal microcircuits, but how these detailed properties of individual neurons give rise to temporal organization of spatial memories remains unclear. We present a model of the hippocampal CA1 microcircuit based on observed biophysical properties of pyramidal cells and six types of inhibitory interneurons: axo‐axonic, basket, bistratistified, neurogliaform, ivy, and oriens lacunosum‐moleculare cells. The model simulates a virtual rat running on a linear track. Excitatory transient inputs come from the entorhinal cortex (EC) and the CA3 Schaffer collaterals and impinge on both the pyramidal cells and inhibitory interneurons, whereas inhibitory inputs from the medial septum impinge only on the inhibitory interneurons. Dopamine operates as a gate‐keeper modulating the spatial memory flow to the PC distal dendrites in a frequency‐dependent manner. A mechanism for spike‐timing‐dependent plasticity in distal and proximal PC dendrites consisting of three calcium detectors, which responds to the instantaneous calcium level and its time course in the dendrite, is used to model the plasticity effects. The model simulates the timing of firing of different hippocampal cell types relative to theta oscillations, and proposes functional roles for the different classes of the hippocampal and septal inhibitory interneurons in the correct ordering of spatial memories as well as in the generation and maintenance of theta phase precession of pyramidal cells (place cells) in CA1. The model leads to a number of experimentally testable predictions that may lead to a better understanding of the biophysical computations in the hippocampus and medial septum. © 2012 Wiley Periodicals, Inc.     

Phase relationship between hippocampal place units and the EEG theta rhythm

Many complex spike cells in the hippocampus of the freely moving rat have as their primary correlate the animal's location in an environment (place cells). In contrast, the hippocampal electroer cephalograph theta pattern of rhythmical waves (7–12 Hz) is better correlated with a class of movements that change the rat's location in an environment. During movement through the place field, the complex spike cells often fire in a bursting pattern with an interburst frequency in the same range as the concurrent electroencephalograph theta. The present study examined the phase of the theta wave at which the place cells fired. It was found that firing consistently began at a particular phase as the rat entered the field but then shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This precession of the phase ranged from 100° to 355° in different cells. The effect appeared to be due to the fact that individual cells had a higher interburst rate than the theta frequency. The phase was highly correlated with spatial location and less well correlated with temporal aspects of behavior, such as the time after place field entry. These results have implications for several aspects of hippocampal function. First, by using the phase relationship as well as the firing rate, place cells can improve the accuracy of place coding. Second, the characteristics of the phase shift constrain the models that define the construction of place fields. Third, the results restrict the temporal and spatial circumstances under which synapses in the hippocampus could be modified.     

Stochastic resonance in the hippocampal CA3–CA1 model: a possible memory recall mechanism

Stochastic resonance (SR) in a hippocampal network model was investigated. The hippocampal model consists of two layers, CA3 and CA1. Pyramidal cells in CA3 are connected to pyramidal cells in CA1 through Schaffer collateral synapses. The CA3 network causes spontaneous irregular activity (broadband spectrum peaking at around 3 Hz), while the CA1 network does not. The activity of CA3 causes membrane potential fluctuations in CA1 pyramidal cells. The CA1 network also receives a subthreshold signal (2.5 or 50 Hz) through the perforant path (PP). The subthreshold PP signals can fire CA1 pyramidal cells in cooperation with the membrane potential fluctuations that work as noise. The firing of the CA1 network shows typical features of SR. When the frequency of the PP signal is in the gamma range (50 Hz), SR that takes place in the present model shows distinctive features. 50 Hz firing of CA1 pyramidal cells is modulated by the membrane potential fluctuations, resulting in bursts. Such burst firing in the CA1 network, which resembles the firing patterns observed in the real hippocampal CA1, improves performance of subthreshold signal detection in CA1. Moreover, memory embedded at Schaffer collateral synapses can be recalled by means of SR. When Schaffer collateral synapses in subregions of CA1 are augmented three-fold as a memory pattern, pyramidal cells in the subregions respond to the subthreshold PP signal due to SR, while pyramidal cells in the rest of CA1 do not fire.     

Somatosensory stimulation suppresses the excitability of pyramidal cells in the hippocampal CA1 region in rats

The hippocampal region of the brain is important for encoding environment inputs and memory formation. However, the underlying mechanisms are unclear. To investigate the behavior of indi-vidual neurons in response to somatosensory inputs in the hippocampal CA1 region, we recorded and analyzed changes in local ifeld potentials and the ifring rates of individual pyramidal cells and interneurons during tail clamping in urethane-anesthetized rats. We also explored the mechanisms underlying the neuronal responses. Somatosensory stimulation, in the form of tail clamping, chan-ged local ifeld potentials into theta rhythm-dominated waveforms, decreased the spike ifring of py-ramidal cells, and increased interneuron ifring. In addition, somatosensory stimulation attenuated orthodromic-evoked population spikes. These results suggest that somatosensory stimulation sup-presses the excitability of pyramidal cells in the hippocampal CA1 region. Increased inhibition by local interneurons might underlie this effect. These ifndings provide insight into the mechanisms of signal processing in the hippocampus and suggest that sensory stimulation might have thera-peutic potential for brain disorders associated with neuronal hyperexcitability.     

Preserved spatial coding in hippocampal CA1 pyramidal cells during reversible suppression of CA3c output: evidence for pattern completion in hippocampus

Medial septal modulation of hippocampal single-unit activity was examined by assessing the behavioral and physiological consequences of reversibly inactivating the medial septum via microinjection of a local anesthetic (tetracaine) in freely behaving rats trained to solve a working memory problem on a radial maze. Reversible septal inactivation resulted in a dramatic, but temporary (15-20 min), impairment in choice accuracy. In addition, movement-induced theta (theta) modulation of the hippocampal EEG was eliminated. Septal injection of tetracaine also produced a significant reduction in location-specific firing by hilar/CA3c complex-spike cells (about 50%), with no significant change in the place-specific firing properties of CA1 complex-spike units. The mean spontaneous rates of stratum granulosum and CA1 theta cells were temporarily reduced by about 50% following septal injection of tetracaine. Although there was a significant reduction in the activities of inhibitory interneurons (theta cells) in CA1, there was no loss of spatial selectivity in the CA1 pyramidal cell discharge patterns. We interpret these results as support for the proposal originally put forth by Marr (1969, 1971) that hippocampal circuits perform pattern completion on fragmentary input information as a result of a normalization operation carried out by inhibitory interneurons. A second major finding in this study was that location specific firing of CA1 cells can be maintained in the virtual absence of the hippocampal theta-rhythm.     

Sustained activation of hippocampal pyramidal cells by 'space clamping' in a running wheel

In contrast to sensory cortical areas of the brain, the relevant physiological inputs to the hippocampus, leading to selective activation of pyramidal cells, are largely unknown. Pyramidal cells are thought to be phasically activated by spatial cues and a variety of sensory and motor stimuli. Here, we used a behavioural ‘space clamp’ method, which involved the confinement of the actively running animal in a defined position in space (running wheel) and kept sensory inputs constant. Twelve percent of the recorded CA1 pyramidal cells were selectively active while the rat was running in the wheel. Cell firing was specific to the direction of running and disappeared after rotating the recording apparatus. The discharge frequency of pyramidal cells and interneurons was sustained as long as the rat ran continuously in the wheel. Furthermore, the discharge frequency of pyramidal cells and interneurons increased with increasing running velocity, even though the frequency of hippocampal theta waves remained constant. The discharge frequency of some ‘wheel-related’ pyramidal cells could increase more than 10-fold between 10 and 100 cm/s, whereas the firing rate of ‘non-wheel’ cells remained constantly low. We hypothesize that: (i) a necessary condition for place-specific discharge of hippocampal pyramidal cells is the presence of theta oscillation; and (ii) relevant stimuli can tonically and selectively activate hippocampal pyramidal cells as long as theta activity is present.     

A computational study on plasticity during theta cycles at Schaffer collateral synapses on CA1 pyramidal cells in the hippocampus

Cellular activity in the CA1 area of the hippocampus waxes and wanes at theta frequency (4–8 Hz) during exploratory behavior of rats. Perisomatic inhibition onto pyramidal cells tends to be strongest out of phase with pyramidal cell activity, whereas dendritic inhibition is strongest in phase with pyramidal cell activity. Synaptic plasticity also varies across the theta cycle, from strong long‐term potentiation (LTP) to long‐term depression (LTD), putatively corresponding to encoding and retrieval phases for information patterns encoded by pyramidal cell activity (Hasselmo et al. (2002a) Neural Comput 14:793–817). The mechanisms underpinning the phasic changes in plasticity are not clear, but it is likely that inhibition plays a role by affecting levels of electrical activity and calcium concentration at synapses. We explore the properties of synaptic plasticity during theta at Schaffer collateral synapses on CA1 pyramidal neurons and the influence of spatially and temporally targeted inhibition using a detailed multicompartmental model of the CA1 pyramidal neuron microcircuit and a phenomenological model of synaptic plasticity. The results suggest CA3‐CA1 synapses are potentiated on one phase of theta due to high calcium levels provided by paired weak CA3 and layer III entorhinal cortex (EC) inputs even when somatic spiking is inhibited by perisomatic interneuron activity. Weak CA3 inputs alone induce lower calcium transients and result in depression of the CA3‐CA1 synapses. These synapses are depressed if activated in phase with dendritic inhibition as strong CA3 inputs alone are not able to cause high calcium in this theta phase even though the CA1 pyramidal neuron shows somatic spiking. Dendritic inhibition acts as a switch that prevents LTP and promotes LTD during the retrieval phases of the theta rhythm in CA1 pyramidal cell. This may be important for not overly reinforcing recalled memories and in forgetting no longer relevant memories. © 2014 Wiley Periodicals, Inc.