Apical Dendrites In CA1 Research Articles

Long-term depression induction and maintenance across regions of the apical branch of CA1 dendrites.

Well known as the center for learning and memory, hippocampus is the crucial brain region to study synaptic plasticity in the context of cellular fundamental mechanisms such as long-term depression (LTD) and long-term potentiation (LTP). However, despite years of extensive research, the key to our LTD queries and their induction mechanisms has not been fully understood. Previously, we reported the induction of late-LTD (L-LTD) in the distally located synapses of apical branch of hippocampal CA1 dendrites using strong low-frequency stimulation (SLFS). In contrast synapses at the proximal site could not express L-LTD. Thus, in the present study, we wanted to investigate whether or not synapses of apical dendritic branch at the proximal location could induce and maintain LTD and its related properties in in vitro rat hippocampal slices. Results indicated that the SLFS in the distal and proximal region triggered the plasticity related proteins (PRP) synthesis in both regions, as evident by the induction and maintenance of L-LTD in the distal region by virtue of synaptic and cross-tagging. In addition, the application of emetine at the time of proximal input stimulation prevented the transition of early-LTD (E-LTD) into L-LTD at the distal region, proving PRP synthesis at the proximal site. Further, it was observed that weak low-frequency stimulation (WLFS) could induce E-LTD in the proximal region along with LTD-specific tag-setting at the synapses. In conclusion, the current study suggests unique findings that the synaptic and cross-tagging mediate L-LTD expression is maintained in the proximal location of hippocampus apical CA1 dendrites.

Estradiol rapidly increases GluA2-mushroom spines and decreases GluA2-filopodia spines in hippocampus CA1.

Hippocampal dendritic spine density rapidly increases following estradiol (E2 ) treatment, but the types of spines and trafficking of synaptic markers have received little investigation. We assessed rapid effects of E2 over time on the density of four spine types (stubby, filopodial, long thin, and mushroom) and trafficking of AMPA receptor subunit GluA2 and PSD95 on tertiary, apical dendrites in CA1. Castrated male rats received 20 μgkg-1 of E2 or vehicle and were sacrificed 30 or 120 min later. Images of Golgi-Cox impregnated and PSD95/GluA2 stained dendrites were captured under the confocal microscope and quantified with IMARIS-XT. Stubby and filopodial spine densities did not change following treatment. Long-thin spines significantly decreased at 30 min while mushroom spines significantly increased at 120 min. GluA2, PSD95, and GluA2/PSD95 colocalization levels in stubby or long thin spines did not change, but filopodial spines had significantly reduced GluA2 levels at 30 min. Mushroom spines showed significantly increased levels for GluA2, PSD95 and GluA2/PSD95 colocalization at 120 min. Because GluA2 is important for memory consolidation, current results present novel data suggesting that trafficking of GluA2 to mushroom spines provides one mechanism contributing to estradiol's ability to enhance learning and memory by the PI3 signaling pathway.

Separation increases passive stress-coping behaviors during forced swim and alters hippocampal dendritic morphology in California mice

Individuals within monogamous species form bonds that may buffer against the negative effects of stress on physiology and behavior. In some species, involuntary termination of the mother-offspring bond results in increased symptoms of negative affect in the mother, suggesting that the parent-offspring bond may be equally as important as the pair bond. To our knowledge, the extent to which affect in paternal rodents is altered by involuntary termination of the father-offspring bond is currently unknown. Here, we investigated to what extent separation and paternal experience alters passive stress-coping behaviors and dendritic morphology in hippocampal subfields of California mice (Peromyscus californicus). Irrespective of paternal experience, separated mice displayed shorter latencies to the first bout of immobility, longer durations of immobility, and more bouts of immobility than control (non-separated) mice. This effect of separation was exacerbated by paternal experience in some measures of behavioral despair—separation from offspring further decreased the latency to immobility and increased bouts of immobility. In the dentate gyrus, separation reduced dendritic spine density regardless of paternal experience. Increased spine density was observed on CA1 basal, but not apical, dendrites following paternal experience. Regardless of offspring presence, fatherhood was associated with reduced apical dendritic spine density in area CA3 of the hippocampus. Separation enhanced complexity of both basal and apical dendrites in CA1, while fatherhood reduced dendritic complexity in this region. Our data suggest that forced dissolution of the pair bond induces passive stress-coping behaviors and contributes to region-specific alterations in hippocampal structure in California mouse males.

Constitutive activation of CREB in mice enhances temporal association learning and increases hippocampal CA1 neuronal spine density and complexity

Transcription factor CREB is believed to play essential roles in the formation of long-term memory (LTM), but not in learning and short-term memory (STM). Surprisingly, we previously showed that transgenic mice expressing a dominant active mutant of CREB (DIEDML) in the forebrain (DIEDML mice) demonstrated enhanced STM and LTM in hippocampal-dependent, rapid, one-trial learning tasks. Here we show that constitutive activation of CREB enhances hippocampal-dependent learning of temporal association in trace fear conditioning and delayed matching-to-place tasks. We then show that in DIEDML mice the apical tuft dendrites of hippocampal CA1 pyramidal neurons, required for temporal association learning, display increased spine density, especially of thin spines and of Homer1-negative spines. In contrast, the basal and apical oblique dendrites of CA1 neurons, required for rapid one-trial learning, show increased density of thin, stubby, and mushroom spines and of Homer1-positive spines. Furthermore, DIEDML mice showed increased dendritic complexity in the proximal portion of apical CA1 dendrites to the soma. In contrast, forebrain overexpression of CaMKIV, leading to enhanced LTM but not STM, show normal learning and CA1 neuron morphology. These findings suggest that dendritic region-specific morphological changes in CA1 neurons by constitutive activation of CREB may contribute to improved learning and STM.

Different compartments of apical CA1 dendrites have different plasticity thresholds for expressing synaptic tagging and capture

The consolidation process from short- to long-term memory depends on the type of stimulation received from a specific neuronal network and on the cooperativity and associativity between different synaptic inputs converging onto a specific neuron. We show here that the plasticity thresholds for inducing LTP are different in proximal and distal compartments of apical dendrites. In addition, we show interactions between the proximal and distal compartments of the apical dendrites by providing evidence that even a subthreshold stimulus can activate plasticity-related proteins, such as PKMζ, enabling associativity between two distinct dendritic compartments in apical dendrites to occur.

Protein kinase Mζ is essential for the induction and maintenance of dopamine-induced long-term potentiation in apical CA1 dendrites

Dopaminergic D1/D5-receptor-mediated processes are important for certain forms of memory as well as for a cellular model of memory, hippocampal long-term potentiation (LTP) in the CA1 region of the hippocampus. D1/D5-receptor function is required for the induction of the protein synthesis-dependent maintenance of CA1-LTP (L-LTP) through activation of the cAMP/PKA-pathway. In earlier studies we had reported a synergistic interaction of D1/D5-receptor function and N-methyl-D-aspartate (NMDA)-receptors for L-LTP. Furthermore, we have found the requirement of the atypical protein kinase C isoform, protein kinase Mζ (PKMζ) for conventional electrically induced L-LTP, in which PKMζ has been identified as a LTP-specific plasticity-related protein (PRP) in apical CA1-dendrites. Here, we investigated whether the dopaminergic pathway activates PKMζ. We found that application of dopamine (DA) evokes a protein synthesis-dependent LTP that requires synergistic NMDA-receptor activation and protein synthesis in apical CA1-dendrites. We identified PKMζ as a DA-induced PRP, which exerted its action at activated synaptic inputs by processes of synaptic tagging.

Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in SlicesIn Vitro

Long-term potentiation (LTP) is a cellular correlate for memory formation, which requires the dynamic changes of the actin cytoskeleton. As shown by others, the polymerization of the actin network is important for early stages of LTP. Here, we investigated the role of actin dynamics in synaptic tagging and particularly in the induction of protein synthesis-dependent late-LTP in the CA1 region in hippocampal slices in vitro. We found that the inhibition of actin polymerization affects protein synthesis-independent early-LTP, prevents late-LTP, and interferes with synaptic tagging in apical dendrites of hippocampal CA1. The transformation of early-LTP into late-LTP was blocked by the application of the structurally different actin polymerization inhibitors latrunculin A or cytochalasin D. We suggest that the actin network is required for early "housekeeping" processes to induce and maintain early-LTP. Furthermore, inhibition of actin dynamics negatively interacts with the setting of the synaptic tagging complex. We propose actin as a further tag-specific molecule in apical CA1 dendrites where it is directly involved in the tagging/capturing machinery. Consequently, inhibition of the actin network prevents the interaction of tagging complexes with plasticity-related proteins. This results in the prevention of late-LTP by inhibition of the actin network during LTP induction.

Modulation of extracellular monoamine transmitter concentrations in the hippocampus after weak and strong tetanization of the perforant path in freely moving rats

Hippocampal long-term potentiation (LTP) is considered as a cellular model of memory formation. Specific, electrical weak tetanization of distinct afferents such as the medial perforant path results in a short-lasting, protein synthesis-independent early-LTP (up to 4 h) within the dentate gyrus. A stronger tetanization leads to late-LTP (> 4 h), which is protein synthesis-dependent and requires heterosynaptic activation during its induction, the latter of which can be provided by afferents from cortical brain regions or subcortical nuclei during memory formation in the behaving animal. In particular, noradrenaline (NA) is required for late-LTP in the dentate gyrus and dopamine for late-LTP in the apical CA1-dendrites. However, little is known about the concentrations and temporal dynamics of such neuromodulators like NA, serotonin (5-HT) and dopamine (DA) during LTP. We now implemented the microdialysis method to study this topic after stimulating the dentate gyrus in more detail. A weak tetanus of the perforant path, which normally leads to early-LTP, transiently but significantly decreased the concentration of NA (3 h) and increased the concentration of 5-HT (about 2 h) and DA (about 1 h) in the hippocampus. A strong tetanus, normally resulting in late-LTP, increased concentrations of NA and DA significantly and long-lasting (for about 5 h), whereas 5-HT concentration was increased with a delay (after about 30 min) and only for a short time (30 min). Thus different stimulation protocols resulted in different release patterns of neuromodulators, that may support discriminative processing of incoming information in the hippocampus.

Identification of Compartment- and Process-Specific Molecules Required for “Synaptic Tagging” during Long-Term Potentiation and Long-Term Depression in Hippocampal CA1

Protein synthesis-dependent forms of hippocampal long-term potentiation (late LTP) and long-term depression (late LTD) are prominent cellular mechanisms underlying memory formation. Recent data support the hypothesis that neurons store relevant information in dendritic functional compartments during late LTP and late LTD rather than in single synapses. It has been suggested that processes of "synaptic tagging" are restricted to such functional compartments. Here, we show that in addition to apical CA1 dendrites, synaptic tagging also takes place within basal CA1 dendritic compartments after LTP induction. We present data that tagging in the basal dendrites is restricted to these compartments. Plasticity-related proteins, partially nonspecific to the locally induced process, are synthesized in dendritic compartments and then captured by local, process-specific synaptic tags. We support these findings in two ways: (1) late LTP/LTD, locally induced in apical or basal (late LTP) dendrites of hippocampal CA1 neurons, does not spread to the basal or apical compartment, respectively; (2) the specificity of the synaptic plasticity event is achieved by the activation of process- and compartment-specific synaptic tag molecules. We have identified calcium/calmodulin-dependent protein kinase II as the first LTP-specific and extracellular signal-regulated kinase 1/2 as LTD-specific tag molecules in apical dendritic CA1 compartments, whereas either protein kinase A or protein kinase Mzeta mediates LTP-specific tags in basal dendrites.

Basal versus apical dendritic long-term potentiation of commissural afferents to hippocampal CA1: a current-source density study

Current-source density analysis was used to estimate the magnitude of the synaptic excitation at the basal and apical dendritic synapses of CA1 following commissural stimulation in the urethane-anesthetized rat, before and after a theta-frequency patterned primed burst tetanus. Stimulation of the contralateral CA3 or the contralateral CA1 stratum oriens excited both the basal and apical dendrites in CA1 about equally. However, primed burst tetanization of the contralateral CA3 or CA1 stratum oriens resulted in significant long-term potentiation (LTP) only at the basal dendrites and not at the apical dendrites. Stimulation of the contralateral CA1 stratum radiatum excited the apical dendrites more than the basal dendrites of CA1, but tetanization of this contralateral site gave little change in the apical or basal dendritic excitation. Tetanization of the contralateral CA1 stratum radiatum after an intraventricular administration of bicuculline, a GABAA antagonist, however, resulted in significant LTP at both the apical and basal dendrites. It was concluded that, in the intact hippocampus in vivo, the threshold for LTP at the commissural apical dendritic synapse was high in comparison to that at the basal dendritic synapse and this high threshold may be partly caused by inhibitory interneurons that predominantly synapsed on the apical dendrites. Thus, the basal and apical dendrites of the CA1 pyramidal cells are not equal in their propensity for long-term plasticity.

Field potentials in rat hippocampus: Monosynaptic nature and heterosynaptic post-tetanic potentiation

Subicular, commisural, and fornical stimulation evoked large field responses in the dentate gyrus and dorsal hippocampus of rats. Hippocampal responses were negative above and positive below the upper third of apical dendrites in CA1, CA2, and CA3; the application of a pressing foot on the alveus resulted in a distortion of this polarity pattern. Since a compound action potential was found in the fornix during the rising phase of hippocampal field responses, it was concluded that the latter correlated with excitation of pyramidal cells. The following frequency of dentate and hippocampal potentials was high (up to 125/sec) and similar for both; thus, it was concluded that both were monosynaptic responses. On the basis of excluding several impossible mechanisms, hippocampal field potentials were attributed to a flow of cations, through the extracellular clefts, from the stratum pyramidale down to the stratum radiale. Hippocampal- and dentate-evoked potentials suffered post-tetanic potentiation; in the case of hippocampal responses, this was both homo- and heterosynaptic. The possible relevance of the latter to mechanisms of learning, and the possible genesis of both by (K +) 0 accumulation were discussed.

Location and identification of excitatory synapses on hippocampal pyramidal cells.

1. In rabbits and cats anaesthetized by urethane-chloralose or pentobarbital sodium, stimulation of the commissural afferent pathway produced a negative field potential with maximal amplitude in the CA3 basal dendritic layer, and with a latency indicative of monosynaptic activation of excitatory synapses on the basal dendrites. 2. Mossy fibre stimulation resulted in a similar field potential restricted to the mossy fibre layer. Comparable negative field potentials were found in the layer of apical dendrites in CA1 in response to commissural and Schaffer collateral stimulation, suggesting a dendritic location of these synapses. 3. All negative field potentials grew in amplitude on tetanic stimulation, to produce large extracellular spikes, indicating their association with excitatory synaptic activity. 4. Usually, all pathways employed failed to produce EPSPs on single shock stimulation, in spite of their capability of discharging the cells, suggesting that the synaptic depolarization takes place at some distance from the soma. 5. Electron microscopy of degenerated commissural afferent fibres showed them to make contact with spines or the smooth surface of thin dendrites. The indentification of the postsynaptic element as pyramidal cell dendrite was ascertained. The mossy fibres end on ramified dendritic spines in CA3. 6. By comparison with normal electron micrographs, all the pathways, shown physiologically to be excitatory, terminate on thin dendrites, the contacts being of type 1.