Muscarinic Acetylcholine Receptor Activation Prevents Disinhibition-Mediated LTP in the Hippocampus.

Muscarinic acetylcholine receptor activation prevents disinhibition-mediated LTP in the hippocampus.

Front Cell Neurosci. 2013; 7: 16
Takkala P, Woodin MA

Disinhibition-mediated long-term potentiation (LTP) in the CA1 region of the hippocampus involves GABAergic synaptic plasticity at feedforward inhibitory inputs, resulting in the reduced shunting of glutamatergic excitatory currents. The GABAergic plasticity which underlies disinhibition-mediated LTP results from a Ca-dependent decrease in the activity of the K-Cl cotransporter (KCC2), depolarizing the reversal potential for GABA receptor-mediated currents (E), thereby attenuating inhibition. Muscarinic acetylcholine receptor (mAChR) activation has previously been shown to regulate classic glutamatergic LTP, modulate intracellular [Ca] and signaling, and facilitate the excitability of GABAergic interneurons in the CA1. Based on these effects, and the ability of mAChR activation to regulate CA1 pyramidal neuron KCC2 expression, we proposed that mAChR activation would modulate disinhibition-mediated LTP. To test this prediction, we made whole cell recordings from CA1 pyramidal neurons in hippocampal slices. Disinhibition-mediated LTP was induced using a spike timing-dependent plasticity (STDP) protocol, which involved coincident pre-synaptic stimulation and post-synaptic current injection (at 5 Hz for 60 s). We found that mAChR activation via carbachol (CCh) prevented the induction of disinhibition-mediated LTP. Moreover, in the presence of CCh, E failed to depolarize following plasticity induction. Lastly, we recorded the paired-pulse ratio (PPR) during the induction of disinhibition-mediated LTP and found that in the presence of CCh, plasticity induction induced a significant paired-pulse depression. This suggests that pre-synaptic mAChR activation may prevent the post-synaptic expression of disinhibition-mediated LTP. HubMed – depression


Public stigma associated with psychosis risk syndrome in a college population: implications for peer intervention.

Psychiatr Serv. 2013 Mar 1; 64(3): 284-8
Yang LH, Anglin DM, Wonpat-Borja AJ, Opler MG, Greenspoon M, Corcoran CM

This study compared stigma associated with the psychosis risk label and diagnostic labels for nonpsychotic and psychotic mental disorders among young adult peers.Urban college respondents (N=153) read an experimental vignette describing a young adult experiencing prodromal symptoms who was randomly assigned a diagnostic label (major depression, generalized anxiety disorder, schizophrenia, or psychosis risk with and without accurate information about the psychosis risk label) and answered questions about stigma toward the individual in the vignette.Compared with labels for nonpsychotic disorders, schizophrenia elicited more negative stereotyping and the at-risk label invoked greater social distance and less willingness to help. Any increased social distance appeared to be reduced by accurate information about the at-risk state. No differences in stigma were found for the psychosis risk and schizophrenia labels.The psychosis risk label alone appeared to evoke greater status loss and discrimination. Accurate information may minimize some stigmatizing attitudes among college peers. HubMed – depression