LTP Maintenance Research Articles

Cholinergic afferents to the locus coeruleus and noradrenergic afferents to the medial septum mediate LTP-reinforcement in the dentate gyrus by stimulation of the amygdala

Transient long-term potentiation (E-LTP) can be transformed into a long-lasting LTP (L-LTP) in the dentate gyrus (DG) by behavioral stimuli with high motivational content. Previous research from our group has identified several brain structures, such as the basolateral amygdala (BLA), the locus coeruleus (LC), the medial septum (MS) and transmitters as noradrenaline (NA) and acetylcholine (ACh) that are involved in these processes. Here we have investigated the functional interplay among brain structures and systems which result in the conversion of a E-LTP into a L-LTP (reinforcement) by stimulation of the BLA (BLA-R). We used topical application of specific drugs into DG, and other targets, while following the time course of LTP induced by stimulation of the perforant pathway (PP) to study their specific contribution to BLA-R. One injection cannula, a recording electrode in the DG and stimulating electrodes in the PP and the BLA were stereotactically implanted one week before electrophysiological experiments. Topical application of atropine or propranolol into the DG blocked BLA-R in both cases, but the effect of propranolol occurred earlier, suggesting a role of NA within the DG during an intermediate stage of LTP maintenance. The injection of lidocaine into the LC abolished BLA-R indicating that the LC is part of the functional neural reinforcing system. The effect on the LC is mediated by cholinergic afferents because application of atropine into the LC produced the same effect. Injection of lidocaine inactivating the MS also abolished BLA-R. This effect was mediated by noradrenergic afferents (probably from the LC) because the application of propranolol into the MS prevented BLA-R. These findings suggest a functional loop for BLA-R involving cholinergic afferents to the LC, a noradrenergic projection from the LC to the DG and the MS, and finally, the cholinergic projection from the MS to the DG.

Comparison of hippocampal LTP induction and maintenance between monkeys and rodents

Comparison of hippocampal LTP induction and maintenance between monkeys and rodents

Increased Ethanol Resistance and Consumption in Eps8 Knockout Mice Correlates with Altered Actin Dynamics

Dynamic modulation of the actin cytoskeleton is critical for synaptic plasticity, abnormalities of which are thought to contribute to mental illness and addiction. Here we report that mice lacking Eps8, a regulator of actin dynamics, are resistant to some acute intoxicating effects of ethanol and show increased ethanol consumption. In the brain, the N-methyl-D-aspartate (NMDA) receptor is a major target of ethanol. We show that Eps8 is localized to postsynaptic structures and is part of the NMDA receptor complex. Moreover, in Eps8 null mice, NMDA receptor currents and their sensitivity to inhibition by ethanol are abnormal. In addition, Eps8 null neurons are resistant to the actin-remodeling activities of NMDA and ethanol. We propose that proper regulation of the actin cytoskeleton is a key determinant of cellular and behavioral responses to ethanol.

LTP: AMPA receptors trading places

Many forms of LTP involve insertion of new postsynaptic AMPA receptors. Plant et al. now report transient insertion of Ca2+-permeable AMPA receptors after LTP induction, and find their activation is required for LTP maintenance.

The Rho-Specific GEF Lfc Interacts with Neurabin and Spinophilin to Regulate Dendritic Spine Morphology

Neurabin and spinophilin are homologous protein phosphatase 1 and actin binding proteins that regulate dendritic spine function. A yeast two-hybrid analysis using the coiled-coil domain of neurabin revealed an interaction with Lfc, a Rho GEF. Lfc was highly expressed in brain, where it interacted with either neurabin or spinophilin. In neurons, Lfc was largely found in the shaft of dendrites in association with microtubules but translocated to spines upon neuronal stimulation. Moreover, expression of Lfc resulted in reduction in spine length and size. Both the translocation and the effect on spine morphology depended on the coiled-coil domain of Lfc. Coexpression of neurabin or spinophilin with Lfc resulted in their clustering together with F-actin, a process that depended on Rho activity. Thus, interaction between Lfc and neurabin/spinophilin selectively regulates Rho-dependent organization of F-actin in spines and is a link between the microtubule and F-actin cytoskeletons in dendrites.

A Competitive Game of Synaptic Tag

LTP maintenance is thought to require an activity-dependent "synaptic tag" that allows potentiated synapses to sequester factors necessary for maintenance. In a paper in this issue of Neuron, Fonseca et al. show that synapses can compete with each other for such maintenance factors, so that additional potentiation of one input results in loss of potentiation of another. These data suggest that LTP maintenance is a dynamic and competitive process.

Hippocampal LTP Is Accompanied by Enhanced F-Actin Content within the Dendritic Spine that Is Essential for Late LTP Maintenance In Vivo

The dendritic spine is an important site of neuronal plasticity and contains extremely high levels of cytoskeletal actin. However, the dynamics of the actin cytoskeleton during synaptic plasticity and its in vivo function remain unclear. Here we used an in vivo dentate gyrus LTP model to show that LTP induction is associated with actin cytoskeletal reorganization characterized by a long-lasting increase in F-actin content within dendritic spines. This increase in F-actin content is dependent on NMDA receptor activation and involves the inactivation of actin depolymerizing factor/cofilin. Inhibition of actin polymerization with latrunculin A impaired late phase of LTP without affecting the initial amplitude and early maintenance of LTP. These observations suggest that mechanisms regulating the spine actin cytoskeleton contribute to the persistence of LTP.

Lesioning the fimbria–fornix impairs basolateral amygdala induced reinforcement of LTP in the dentate gyrus

We have recently shown that early-long-term potentiation (LTP) in the dentate gyrus can be reinforced into late LTP by stimulation of the basolateral nucleus of the amygdala [Frey et al., submitted for publication]. The pathways and mechanisms for such interactions are unclear, considering that no direct projection from the amygdala to the dentate gyrus is known. To ascertain the possible mediation of the septo-hippocampal projection we have transected the fimbria–fornix (FF) fiber system in young adult (2 months) male rats. The electrophysiological evaluation a week later showed that the lesion does not modify the effects of pre-stimulation of the basolateral amygdala (BLA) on the induction of LTP at the perforant pathway (PP)-granule cells synapses, but impairs its maintenance 1 h later. This suggests that two different pathways might mediate different aspects of the amygdala–hippocampal interactions. One seemed to be anatomically independent from the FF and might influence LTP induction; while the second, probably through the septo-hippocampal fornical projection appeared important for LTP maintenance.

Interleukin-2 suppresses established long-term potentiation and inhibits its induction in the rat hippocampus

The effects of recombinant interleukin-2 (rIL-2) on teh potentiation of thesynaptic transmission were studied in rat hippocampal slices by using extracellular field potential recordings. The application of rIL-2 inhibited the induction of both short-term (STP) and long-term potentiation LTP) in a dose-dependent manner. In addition, rIL-2 (1000 U/ml) reduced both post-tetanic potentiation (PTP) and LTP maintenance phase. The possible involvement of rIL-2 action on the synaptic potentiation with the enzymatic activity of protein kinase systems is discussed.