Entorhinal cortex (EC) transfers multimodal information to hippocampus CA1 neurons via indirect and direct pathways. By using ChR2-assisted circuit mapping method, in vivo optogenetics and electrophysiology, we show that excitatory projections from lateral entorhinal cortex selectively target a subpopulation of morphologically complex, calbindin-expressing pyramidal cells (cPCs) in CA1, forming a distinct direct circuit that is required for olfactory associative learning. The cPCs develop more selective spiking responses to odor cues during learning. See Li et al., (2017) Nat. Neurosci. [PDF] This work was selected as a cover story [Cover].
By systematically examining various intracortical synapses within layer 4 of the mouse visual cortex, demonstrate that in the developing visual cortical circuit, temporal dynamics of intracortical excitatory synapses are selectively regulated by visual experience prior to the critical period onset, while that of intracortical inhibitory synapses and long-range thalamocortical excitatory synapses remained unchanged. This provides an additional essential circuitmechanism for regulating critical period plasticity aside from the well-known inhibitory threshold mechanism. See Miao et al., (2016) Cell Reports, http://dx.doi.org/10.1016/j.celrep.2016.07.013. [PDF]
Our latest study, collaborated with Dr. Le-ping Cheng's group at ION, CAS, show that the expression of single transcriptor factor Ascl1 alone is sufficient to convert astrocytes directly into functional neurons in the intact mouse brain. The transdifferentiated neurons mature progressively and fully integrate into existing synaptic circuits in the dorsal midbrain, striatum, and neocortex in the postnatal and adult mouse brain. Thus, our work offers potential therapeutic approaches for neural regeneration. See Liu et al. (2015) J. Neurosci., 35(25):9336 –9355. [PDF]
Critical period plasticity describes a developmental process whereby neural circuits are fine-tuned for specific functions. Here, we show that the Rett syndrome protein MeCP2 in GABAergic parvalbumin- expressing neurons is required for maintaining proper inhibitory circuitry functions that underlie the induction of experience-dependent critical period plasticity of the developing visual cortex. The specific locus of cortical synaptic defects caused by MeCP2 loss in inhibitory PV cells was revealed as well. See He et al., (2014) Nat. Commun., 5:5036 doi: 10.1038/ncomms6036. [PDF]
Using in vivo whole-cell recording from the developng mouse V1, we demonstrate that the coincidence of binocular synaptic inputs from the two eyes is a hallmark of the critical period and serves as neural substrates for the induction of experience-dependent ocular dominance plasticity of the developing V1. Computational simulation further suggests the coincident inputs mediates the plasticity via a homeostatic synaptic learning mechanism. See Chen et al., (2014) J. Neurosci., 34(8):2940-2955. [PDF]
Activity-induced synaptic modification provides a cellular basis for developmental refinement of neuronal connections and for the information storage that is associated with learning and memory. Here, we show that at developing hippocamal GABAergic synapses, a bi-directional modification of GABAergic synapses that is induced by repetitive coincident pre- and postsynaptic spiking at different frequenciesand postsynaptic GABA(B)R activation mediates the LTP. See Xu et al., (2008) Nat. Neurosci., 11, 1410 - 1418. [PDF]
The integretion of synaptic inputs at the dendrite determines the neuronal spike ouput. Based on realistic modeling and experiments in rat hippocampal slices, we derived a simple arithmetic rule for spatial summation of concurrent excitatory glutamatergic inputs (E) and inhibitory GABAergic inputs (I). Our rule offers a simple analytical tool for studying E–I integration in pyramidal neurons that incorporates the location specificity of GABAergic shunting inhibition. See Hao et al., (2009) PNAS, 106(51) 21906–21911. [PDF]
We further derive a bilinear spatiotemporal dendritic integration rule, based on asymptotic analysis of a two-compartment passive cable model. The rule is valid for spatiotemporal integration of multiple inputs with arbitrary input time differences and locations at the dendrite. This generalized rule offers an analytic algorithm that could be applied to large-scale simulations of networks of the neuron incorporating dendritic integrations with less computation cost. See Li et al., (2014) PLoS Comput. Biol., 10(12): e1004014. [PDF]