Types Of Long-term Depression Research Articles

Impairment of Select Forms of Spatial Memory and Neurotrophin-Dependent Synaptic Plasticity by Deletion of Glial Aquaporin-4

Aquaporin-4 (AQP4) is the major water channel in the CNS and is primarily expressed in astrocytes. Little is known about the potential for AQP4 to influence synaptic plasticity, although many studies have shown that it regulates the response of the CNS to injury. Therefore, we evaluated long-term potentiation (LTP) and long-term depression (LTD) in AQP4 knock-out (KO) and wild-type mice. KO mice exhibited a selective defect in LTP and LTD without a change in basal transmission or short-term plasticity. Interestingly, the impairment in LTP in KO mice was specific for the type of LTP that depends on the neurotrophin BDNF, which is induced by stimulation at theta rhythm [theta-burst stimulation (TBS)-LTP], but there was no impairment in a form of LTP that is BDNF independent, induced by high-frequency stimulation. LTD was also impaired in KO mice, which was rescued by a scavenger of BDNF or blockade of Trk receptors. TrkB receptors, which mediate effects of BDNF on TBS-LTP, were not altered in KO mice, but p75NTR, the receptor that binds all neurotrophins and has been implicated in some types of LTD, was decreased. The KO mice also exhibited a cognitive defect, which suggests a new role for AQP4 and astrocytes in normal cognitive function. This defect was evident using a test for location-specific object memory but not Morris water maze or contextual fear conditioning. The results suggest that AQP4 channels in astrocytes play an unanticipated role in neurotrophin-dependent plasticity and influence behavior.

Long-term depression induced by local tetanic stimulation in the rat auditory cortex

In sensory cortices, synaptic plasticities such as long-term potentiation (LTP) and long-term depression (LTD) have important roles in the development of neural circuits and sensory information processing. However, the differential roles and mechanisms of the various types of LTP and LTD are not clear. In the present study, we investigated LTP and two types of LTD in slices obtained from the rat auditory cortex. Supragranular field potentials elicited by layer VI stimulation were recorded through a metal electrode. Transsynaptic field potentials exhibited marked LTP after tetanic stimulation (TS, 100 Hz for 1 s) was applied to layer VI. The same field potential components exhibited LTD after low-frequency stimulation (LFS, 1 Hz for 900 s) was applied to layer VI. LTD of supragranular field potentials was also induced by local TS applied to supragranular layers 0.3 mm from the recording site. Neither LTP nor LTD of either type was induced in the presence of 50 μM d-(−)-2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist. However, 500 μM (+)-α-methyl-4-carboxyphenylglycine (MCPG), an antagonist of metabotropic glutamate receptors, had no effect. LTD induced by LFS and that induced by local TS were suppressed in the presence of 3 μM bicuculline, an antagonist of GABA A receptors. Each of these forms of LTD occluded the other. These results and intracellular recordings in supragranular pyramidal neurons during LFS and local TS strongly suggest that the two types of LTD share common neural circuits for their induction.

Synergistic action of GABA‐A and NMDA receptors in the induction of long‐term depression in glutamatergic synapses in the newborn rat hippocampus

We show that activation of GABA(A) receptors (GABA(A)Rs) promotes induction of N-methyl-D-aspartate (NMDA) receptor (NMDAR)-dependent long-term depression (LTD) of glutamatergic synapses in the newborn rat hippocampal area CA1 in a developmentally restricted manner. In the newborn rat hippocampus two mechanistically different types of LTD of glutamatergic synapses could be induced under similar experimental conditions. The form of the LTD induced depended on the stimulation protocol and on the age of the animal. Low-frequency stimulation (1 Hz) with 100 stimuli induced a robust homosynaptic, reversible LTD at postnatal days 2-8 (P2-P8) but not at P14. This LTD was blocked by the NMDAR antagonist AP5 or by the GABA(A)R antagonist picrotoxin. Use of a low-chloride solution in the patch pipette resulting in E(GABA-A) < -70 mV blocked the NMDAR-dependent LTD, whereas clamping the cell to -40 mV during induction rescued it. In addition, it was possible to induce LTD at P14 with 100 stimuli if the cells were clamped to -40 mV during induction. Low-frequency stimulation with 900 stimuli induced a robust homosynaptic, reversible LTD both at P2-P8 and at P14. However, neither AP5 nor picrotoxin affected the LTD induced by 900 pulses at P2-P8. Instead, the 900 stimuli-induced LTD was blocked by the metabotropic glutamate receptor antagonists when co-applied with AP5. We suggest that during the first postnatal week postsynaptic depolarization provided by the activation of GABA(A)Rs shifts the threshold for the LTD induction, making the synapses more prone to activity-induced plasticity. From the second postnatal week onwards, when the GABA(A) responses are already hyperpolarizing, different mechanisms for LTD induction prevail.

Endocannabinoid-Dependent Neocortical Layer-5 LTD in the Absence of Postsynaptic Spiking

Long-term depression (LTD) was induced in neocortical layer 5 pyramidal connections by pairing presynaptic firing with subthreshold postsynaptic depolarization (dLTD) or via a spike-timing protocol (tLTD). Like tLTD, dLTD reduced short-term depression and increased the coefficient of variation consistent with a presynaptic site of expression. Also like tLTD, dLTD was blocked by CB1 cannibinoid receptor blockade and required activation of presumably presynaptic NR2B-containing N-methyl-D-aspartate receptors. The two forms of LTD had identical magnitudes and time courses and occluded one another, and neither depended on frequency. Finally, dLTD shares with tLTD the asymmetric temporal window of induction. In conclusion, the types of LTD induced by these two protocols are indistinguishable, suggesting that the mechanism that underlies tLTD paradoxically does not require postsynaptic spiking: The subthreshold postsynaptic depolarizations of dLTD appear to fully substitute for postsynaptic spiking.

Emerging roles for endocannabinoids in long‐term synaptic plasticity

British Journal of Pharmacology (2003) 140, 781–789. doi:10.1038/sj.bjp.0705466

Associative, bidirectional modifications at the hippocampal mossy fibre-CA3 synapse.

Long-term potentiation (LTP) and long-term depression (LTD) are activity-dependent changes in synaptic strength that may serve as the cellular mechanisms of information storage in the vertebrate brain. The mossy fibre-CA3 synapse displays NMDA (M-methyl-D-aspartate) receptor-independent forms of LTP and LTD that were thought to be non-associative. Here we report that the mossy fibre-CA3 synapse displays each of the known types of LTD in vivo, including associative, heterosynaptic and homosynaptic LTD. These types of LTD are induced when only two of the three conditions necessary for mossy fibre LTP induction are provided. Because some of these conditions can be provided by convergent CA3 afferents, each type of LTD can be induced in an associative manner, which suggests that LTD is involved in associative information storage. Similar to the induction of NMDA receptor-dependent LTD and LTP at other cortical synapses, mossy fibre LTD occurs when synaptic conditions are insufficient to induce LTP, and both LTP and LTD induction are influenced by previous synaptic activity, consistent with the view that common principles govern activity-dependent plasticity at cortical synapses.

Long-term depression in hippocampus.

Long-term depression (LTD) is a lasting decrease in synaptic effectiveness that follows some types of electrical stimulation in the hippocampus. Two broad types of LTD may be distinguished. Heterosynaptic LTD can occur at synapses that are inactive, normally during high-frequency stimulation of a converging synaptic input. Homosynaptic LTD can occur at synapses that are activated, normally at low frequencies. Here we discuss the mechanisms of LTD and their possible relevance to hippocampal function.

Long-Term Depression in Hippocampus

Long-term depression (LTD) is a lasting decrease in synaptic effectiveness that follows some types of electrical stimulation in the hippocampus. Two broad types of LTD may be distinguished. Heterosynaptic LTD can occur at synapses that are inactive, normally during high-frequency stimulation of a converging synaptic input. Homosynaptic LTD can occur at synapses that are activated, normally at low frequencies. Here we discuss the mechanisms of LTD and their possible relevance to hippocampal function.