Brain-derived neurotrophic factor-mediated retrograde signaling required for the induction of long-term potentiation at inhibitory synapses of visual cortical pyramidal neurons

AbstractExposure to humans and experimental animals to loud noises produce cognitive and emotional disorders and recent studies have shown that hippocampal neuronal function is affected by auditory stimulation or deprivation. We have found previously that in the hippocampus of rats exposed to high-intensity sound (110 dB) for one-minute the Schaffer-CA1 long-term potentiation (LTP) is strongly inhibited. Here we investigated possible mechanisms involved in this effect. We found, using c-fos expression, that exposure to 110 dB sound-activated neurons in the CA1 and CA3 hippocampal region. Using electrophysiological recordings in hippocampal slices, we found that both GABAergic and glutamatergic neurotransmission were unaffected by high-intensity sound stimulation. However, hippocampal brain-derived neurotrophic factor (BDNF), which is involved in promoting hippocampal synaptic plasticity, presented decreased levels in sound-stimulated animals. Perfusion of slices with BDNF revert the inhibition of LTP after a single sound stimulus in comparison to sham-stimulated rats. Furthermore, the perfusion with LM 22A4, a TrkB receptor agonist also rescued LTP from sound-stimulated animals. Our results strongly suggest that the exposure to high-intensity sound inhibits the BDNF production in the hippocampus, which could be a possible mechanism of the inhibition of LTP by high-intensity sound exposure.

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Presynaptic Activity and Ca2+ Entry Are Required for the Maintenance of NMDA Receptor–Independent LTP at Visual Cortical Excitatory Synapses

Journal of Neurophysiology ◽

10.1152/jn.00602.2003 ◽

2004 ◽

Vol 92 (2) ◽

pp. 1077-1087 ◽

Cited By ~ 13

Author(s):

Hong Nian Liu ◽

Tohru Kurotani ◽

Ming Ren ◽

Kazumasa Yamada ◽

Yumiko Yoshimura ◽

...

Keyword(s):

Nmda Receptor ◽

Long Term Potentiation ◽

Inhibitory Synapses ◽

Excitatory Synapses ◽

Test Stimulation ◽

Term Potentiation ◽

Pharmacological Blockade ◽

Visual Cortical ◽

P Type

We have shown that some neural activity is required for the maintenance of long-term potentiation (LTP) at visual cortical inhibitory synapses. We tested whether this was also the case in N-methyl-d-aspartate (NMDA) receptor–independent LTP of excitatory connections in layer 2/3 cells of developing rat visual cortex. This LTP occurred after 2-Hz stimulation was applied for 15 min and always persisted for several hours while test stimulation was continued at 0.1 Hz. When test stimulation was stopped for 1 h after LTP induction, only one-third of the LTP instances disappeared, but most did disappear under a pharmacological suppression of spontaneous firing, indicating that LTP maintenance requires either evoked or spontaneous activities. LTP was totally abolished by a temporary blockade of action potentials with lidocaine or the removal of extracellular Ca2+ after LTP induction, but it persisted under a voltage clamp of postsynaptic cells or after a temporary blockade of postsynaptic activity with the glutamate receptor antagonist kynurenate, suggesting that LTP maintenance requires presynaptic, but not postsynaptic, firing and Ca2+ entry. More than one-half of the LTP instances were abolished after a pharmacological blockade of P-type Ca2+ channels, whereas it persisted after either L-type or Ni2+-sensitive Ca2+ channel blockades. These results show that the maintenance of NMDA receptor–independent excitatory LTP requires presynaptic firing and Ca2+ channel activation as inhibitory LTP, although the necessary level of firing and Ca2+ entry seems lower for the former than the latter and the Ca2+ channel types involved are only partly the same.

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