The Journal of neuroscience : the official journal of the Society for Neuroscience
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The cannabinoid CB1 receptor system is critically involved in the control of associative fear memory formation within the amygdala-prefrontal cortical pathway. The CB1 receptor is found in high concentrations in brain structures that are critical for emotional processing, including the basolateral amygdala (BLA) and the prelimbic division (PLC) of the medial prefrontal cortex (mPFC). However, the precise role of CB1 receptor transmission within the BLA during the processing of fear memory is not fully understood. ⋯ In addition, pharmacological inactivation of the mPFC before intra-BLA CB1 activation blocked CB1-receptor-mediated potentiation of fear memory formation. In vivo single-unit electrophysiological recordings within the PLC revealed that modulation of BLA CB1 receptor transmission strongly influences neuronal activity within subpopulations of PLC neurons, with blockade of intra-BLA CB1 receptor transmission inhibiting spontaneous PLC neuronal activity and activation of CB1 receptors producing robust activation, in terms of neuronal firing frequency and bursting activity. Thus, cannabinoid transmission within the BLA strongly modulates the processing of associative fear memory via functional interactions with PLC neuronal populations.
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Structural and functional plastic changes in the primary somatosensory cortex (S1) have been observed following peripheral nerve injury that often leads to neuropathic pain, which is characterized by tactile allodynia. However, remodeling of cortical connections following injury has been believed to take months or years; this is not temporally correlated with the rapid development of allodynia and S1 hyperexcitability. Here we first report, by using long-term two-photon imaging of postsynaptic dendritic spines in living adult mice, that synaptic connections in the S1 are rewired within days following sciatic nerve ligation through phase-specific and size-dependent spine survival/growth. ⋯ New spines that generated before nerve injury showed volume decrease after injury, whereas more new spines that formed in the early phase of neuropathic pain became persistent and substantially increased their volume during the late phase. Further, preexisting stable spines survived less following injury than controls, and such lost persistent spines were smaller in size than the surviving ones, which displayed long-term potentiation-like enlargement over weeks. These results suggest that peripheral nerve injury induces rapid and selective remodeling of cortical synapses, which is associated with neuropathic pain development, probably underlying, at least partially, long-lasting sensory changes in neuropathic subjects.
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Comparative Study
Diffuse traumatic axonal injury in the mouse induces atrophy, c-Jun activation, and axonal outgrowth in the axotomized neuronal population.
Traumatic axonal injury (TAI) is a consistent component of traumatic brain injury (TBI) and is associated with much of its morbidity. Little is known regarding the long-term retrograde neuronal consequences of TAI and/or the potential that TAI could lead to anterograde axonal reorganization and repair. To investigate the repertoire of anterograde and retrograde responses triggered by TIA, Thy1-YFP-H mice were subjected to mild central fluid percussion injury and killed at various times between 15 min and 28 d post-injury. ⋯ Parallel ultrastructural studies confirmed that these reactive changes are consistent with atrophy in the absence of neuronal death. Concurrent with those events ongoing in the neuronal cell bodies, their downstream axonal segments revealed, as early as 1 d post-injury, morphological changes consistent with reactive sprouting that was accompanied by significant axonal elongation over time. Collectively, these TAI-linked events are consistent with sustained neuronal recovery, an activation of a regenerative genetic program, and subsequent axonal reorganization suggestive of some form of regenerative response.
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Comparative Study
Inflammatory pain unmasks heterosynaptic facilitation in lamina I neurokinin 1 receptor-expressing neurons in rat spinal cord.
Central sensitization in inflammatory pain conditions results in behavioral mechanical hypersensitivity. Specifically, C-fiber-driven spinal hyperexcitability enables A fibers to gain access to specific spinal circuitry, via heterosynaptic facilitatory mechanisms, to mediate mechanical hypersensitivity. However, the precise circuitry engaged is not known. ⋯ Aβ-fiber input to lamina I NK1R(+) neurons was minimal, polysynaptic in nature, and unaltered by CFA inflammation. Additional examination of control neurons revealed that a proportion received silent monosynaptic Aδ-fiber input, suggesting that these may provide the substrate for the novel Aδ inputs observed in CFA inflammation. This inflammation induced unmasking and strengthening of monosynaptic Aδ drive to lamina I NK1R(+) neurons may contribute to the heterosynaptic facilitatory mechanisms underlying mechanical hyperalgesia in inflammatory pain.
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Comparative Study
A portable site: a binding element for 17β-estradiol can be placed on any subunit of a nicotinic α4β2 receptor.
Endogenous steroids can modulate the activity of transmitter-gated channels by directly interacting with the receptor. 17β-Estradiol potentiates activation of neuronal nicotinic α4β2 receptors by interacting with a 4 aa sequence at the extreme C terminus of the α4 subunit, but it is not known whether potentiation requires that the sequence be placed on a specific subunit (e.g., an α4 subunit that is involved in forming an acetylcholine-binding site). By using concatemers of subunits and chimeric subunits, we have found that the C-terminal domain can be moved from the α4 to the β2 subunit and still result in potentiation. In addition, the sequence can be placed on a subunit that contributes to an acetylcholine-binding site or on the structural subunit. The data indicate that this estradiol-binding element is a discrete sequence and suggest that the effect of 17β-estradiol is mediated by actions on single subunits and that the overall consequences for gating occur because of the summation of independent energetic contributions to overall gating of this receptor.