Long-term potentiation in single wide dynamic range neurons induced by noxious stimulation in intact and spinalized rats

Background Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity. Methods Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning. Results The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation. Conclusions Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.

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Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons

PLoS ONE ◽

10.1371/journal.pone.0253642 ◽

2021 ◽

Vol 16 (6) ◽

pp. e0253642

Author(s):

Nicholas P. Vyleta ◽

Jason S. Snyder

Keyword(s):

Entorhinal Cortex ◽

Critical Period ◽

Spatial Information ◽

Dynamic Range ◽

Sensory Information ◽

Long Term Potentiation ◽

Perforant Path ◽

Term Potentiation ◽

Adult Born Neurons

Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer’s pathology. We therefore investigated LTP at LPP inputs both within (4–6 weeks) and beyond (8+ weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3–4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

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N-methyl-D-aspartate receptor blockade during development lowers long-term potentiation threshold without affecting dynamic range of CA3-CA1 synapses

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0831035100 ◽

2003 ◽

Vol 100 (9) ◽

pp. 5503-5508 ◽

Cited By ~ 14

Author(s):

N. Savic ◽

A. Luthi ◽

B. H. Gahwiler ◽

R. A. McKinney

Keyword(s):

Dynamic Range ◽

Long Term Potentiation ◽

Receptor Blockade ◽

Aspartate Receptor ◽

Term Potentiation

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Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons

10.1101/2021.03.15.435460 ◽

2021 ◽

Author(s):

Nicholas P Vyleta ◽

Jason S Snyder

Keyword(s):

Entorhinal Cortex ◽

Critical Period ◽

Spatial Information ◽

Dynamic Range ◽

Sensory Information ◽

Long Term Potentiation ◽

Perforant Path ◽

Term Potentiation ◽

Adult Born Neurons

Critical period plasticity at adult-born neuron synapses is widely believed to contribute to the learning and memory functions of the hippocampus. Experience regulates circuit integration and for a transient interval, until cells are ~6 weeks old, new neurons display enhanced long-term potentiation (LTP) at afferent and efferent synapses. Since neurogenesis declines substantially with age, this raises questions about the extent of lasting plasticity offered by adult-born neurons. Notably, however, the hippocampus receives sensory information from two major cortical pathways. Broadly speaking, the medial entorhinal cortex conveys spatial information to the hippocampus via the medial perforant path (MPP), and the lateral entorhinal cortex, via the lateral perforant path (LPP), codes for the cues and items that make experiences unique. While enhanced critical period plasticity at MPP synapses is relatively well characterized, no studies have examined long-term plasticity at LPP synapses onto adult-born neurons, even though the lateral entorhinal cortex is uniquely vulnerable to aging and Alzheimer's pathology. We therefore investigated LTP at LPP inputs both within (4-6 weeks) and beyond (8+ weeks) the traditional critical period. At immature stages, adult-born neurons did not undergo significant LTP at LPP synapses, and often displayed long-term depression after theta burst stimulation. However, over the course of 3-4 months, adult-born neurons displayed increasingly greater amounts of LTP. Analyses of short-term plasticity point towards a presynaptic mechanism, where transmitter release probability declines as cells mature, providing a greater dynamic range for strengthening synapses. Collectively, our findings identify a novel form of new neuron plasticity that develops over an extended interval, and may therefore be relevant for maintaining cognitive function in aging.

Download Full-text