Bachelor of Science, Jilin University (2008)
Doctor of Philosophy, Beijing Normal University (2013)
Liqun Luo, Postdoctoral Faculty Sponsor
Presynaptic Partners of Dorsal Raphe Serotonergic and GABAergic Neurons
2014; 83 (3): 645-662
The serotonin system powerfully modulates physiology and behavior in health and disease, yet the circuit mechanisms underlying serotonin neuron activity are poorly understood. The major source of forebrain serotonergic innervation is from the dorsal raphe nucleus (DR), which contains both serotonin and GABA neurons. Using viral tracing combined with electrophysiology, we found that GABA and serotonin neurons in the DR receive excitatory, inhibitory, and peptidergic inputs from the same specific brain regions. Embedded in this overall similarity are important differences. Serotonin neurons are more likely to receive synaptic inputs from anterior neocortex while GABA neurons receive disproportionally higher input from the central amygdala. Local input mapping revealed extensive serotonin-serotonin as well as GABA-serotonin connectivity with a distinct spatial organization. Covariance analysis suggests heterogeneity of both serotonin and GABA neurons with respect to the inputs they receive. These analyses provide a foundation for further functional dissection of the serotonin system.
View details for DOI 10.1016/j.neuron.2014.06.024
View details for Web of Science ID 000340479100014
Habenula "Cholinergic" Neurons Corelease Glutamate and Acetylcholine and Activate Postsynaptic Neurons via Distinct Transmission Modes
2011; 69 (3): 445-452
Acetylcholine is an important neurotransmitter, and the habenulo-interpeduncular projection is a major cholinergic pathway in the brain. To study the physiological properties of cholinergic transmission in the interpeduncular nucleus (IPN), we used a transgenic mouse line in which the light-gated cation channel ChannelRhodopsin-2 is selectively expressed in cholinergic neurons. Cholinergic axonal terminals were activated by light pulses, and postsynaptic responses were recorded from IPN neurons. Surprisingly, brief photostimulation produces fast excitatory postsynaptic currents that are mediated by ionotropic glutamate receptors, suggesting wired transmission of glutamate. By contrast, tetanic photostimulation generates slow inward currents that are largely mediated by nicotinic acetylcholine receptors, suggesting volume transmission of acetylcholine. Finally, vesicular transporters for glutamate and acetylcholine are coexpressed on the same axonal terminals in the IPN. These results strongly suggest that adult brain "cholinergic" neurons can corelease glutamate and acetylcholine, but these two neurotransmitters activate postsynaptic neurons via different transmission modes.
View details for DOI 10.1016/j.neuron.2010.12.038
View details for Web of Science ID 000287609700007
View details for PubMedID 21315256
- Quantitative Proteomics of Sleep-Deprived Mouse Brains Reveals Global Changes in Mitochondrial Proteins PloS one 2016; 11 (9): e0163500
- Viral-genetic tracing of the input-output organization of a central noradrenaline circuit NATURE 2015; 524 (7563): 88-U180
Natriuretic peptides block synaptic transmission by activating phosphodiesterase 2A and reducing presynaptic PKA activity
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2012; 109 (43): 17681-17686
The heart peptide hormone atrial natriuretic peptide (ANP) regulates blood pressure by stimulating guanylyl cyclase-A to produce cyclic guanosine monophosphate (cGMP). ANP and guanylyl cyclase-A are also expressed in many brain areas, but their physiological functions and downstream signaling pathways remain enigmatic. Here we investigated the physiological functions of ANP signaling in the neural pathway from the medial habenula (MHb) to the interpeduncular nucleus (IPN). Biochemical assays indicate that ANP increases cGMP accumulation in the IPN of mouse brain slices. Using optogenetic stimulation and electrophysiological recordings, we show that both ANP and brain natriuretic peptide profoundly block glutamate release from MHb neurons. Pharmacological applications reveal that this blockade is mediated by phosphodiesterase 2A (PDE2A) but not by cGMP-stimulated protein kinase-G or cGMP-sensitive cyclic nucleotide-gated channels. In addition, focal infusion of ANP into the IPN enhances stress-induced analgesia, and the enhancement is prevented by PDE2A inhibitors. PDE2A is richly expressed in the axonal terminals of MHb neurons, and its activation by cGMP depletes cyclic adenosine monophosphates. The inhibitory effect of ANP on glutamate release is reversed by selectively activating protein kinase A. These results demonstrate strong presynaptic inhibition by natriuretic peptides in the brain and suggest important physiological and behavioral roles of PDE2A in modulating neurotransmitter release by negative crosstalk between cGMP-signaling and cyclic adenosine monophosphate-signaling pathways.
View details for DOI 10.1073/pnas.1209185109
View details for Web of Science ID 000311147800073
View details for PubMedID 23045693