Upregulation of excitatory neurons and downregulation of inhibitory neurons in barrel cortex are associated with loss of whisker inputs
© Zhang et al.; licensee BioMed Central Ltd. 2013
Received: 3 December 2012
Accepted: 28 December 2012
Published: 3 January 2013
Loss of a sensory input causes the hypersensitivity in other modalities. In addition to cross-modal plasticity, the sensory cortices without receiving inputs undergo the plastic changes. It is not clear how the different types of neurons and synapses in the sensory cortex coordinately change after input deficits in order to prevent loss of their functions and to be used for other modalities. We studied this subject in the barrel cortices from whiskers-trimmed mice vs. controls. After whisker trimming for a week, the intrinsic properties of pyramidal neurons and the transmission of excitatory synapses were upregulated in the barrel cortex, but inhibitory neurons and GABAergic synapses were downregulated. The morphological analyses indicated that the number of processes and spines in pyramidal neurons increased, whereas the processes of GABAergic neurons decreased in the barrel cortex. The upregulation of excitatory neurons and the downregulation of inhibitory neurons boost the activity of network neurons in the barrel cortex to be high levels, which prevent the loss of their functions and enhances their sensitivity to sensory inputs. These changes may prepare for attracting the innervations from sensory cortices and/or peripheral nerves for other modalities during cross-modal plasticity.
KeywordsNeural plasticity Neuron Synapse GABA Glutamate Barrel cortex and whisker
Behavioral experiences modify neuronal function and rewire neuronal circuits to change the brain structure and function, i.e., experience-dependent neural plasticity [1–8]. Despite its critical importance in developmental period , the experience-dependent neural plasticity may occur in the adulthood after removing the stabilized processes and shifting the excitation-inhibition balance [10–15]. The experience-dependent neuronal plasticity is believed to play important roles in the memory formation [16–21] and the behavioral rehabilitation [3, 6]. In terms of the molecular mechanism, long-lasting neuronal activities in various experiences triggers the cellular nuclei to transcript certain genes and the cytoplasm to express the proteins relevant to the plasticity at the neurons and synapses through the diversified arrays [7, 22, 23]. How the different types of the neurons and synapses rewire their connections and reset their functions, i.e., cell-specific changes in the experience-dependent neural plasticity, remains an open question to be studied .
In terms of the cellular mechanism underlying experience-dependent neural plasticity, the model of whisker experiences has been used without organ injury. In these studies, trimming whiskers led to the following changes in the barrel cortex, such as alternations in dynamics of excitatory synapses [25, 26], pathway-specific synaptic plasticity [27–30], dendritic reorganizations [31, 32], new spine generation on dendrites [33, 34], zinc-containing neural circuit reorganization [35, 36], and downregulation in cortical responses [37, 38]. These results indicate the crucial roles of synaptic plasticity and circuit rewire in experience-dependent neural plasticity. It remains unclear how the intrinsic properties at the different types of neurons, the signal transmission at the synapses and the morphology of their subcellular compartments in the barrel cortices are coordinately regulated in response to changing sensory experience.
We have investigated this subject in the barrel cortices from whisker-trimmed mice and controls, in which pyramidal neurons were genetically labeled by yellow fluorescent protein and GABAergic cells were labeled by green one. We analyzed the capability of these neurons to convert excitatory inputs into digital spikes and the intrinsic properties mediated by voltage-gated sodium channels (VGSC). We also analyzed the transmissions of glutamatergic and GABAergic synapses. In terms of their morphology, we analyzed their dendritic structure and spines. Our results indicate that the differentiated regulations in the excitatory and inhibitory units as well as the coordinated change in cellular function and morphology are associated with loss of whisker inputs.
The excitatory units in the barrel cortex are upregulated after loss of whisker inputs
Figure 2C illustrates VGSC-mediated threshold potentials (Vts) at pyramidal neurons. Vts values for spikes 1 to 5 are 30.52±1.56, 40.19±1.1, 40.9±1.9, 39.62±1.88 and 39.56±1.39 in the WT neurons (open symbols; n=15), and are 35.52±1.56, 45.1±2, 44.61±1.68, 45.75±1.97 and 46.19±2.19 in the controls (filled, n=16). Vts values for corresponding spikes are significantly lower in the WT neurons than in the controls (p<0.01). Thus, a loss of whisker inputs reduces the threshold for firing spikes at barrel cortical pyramidal neurons.
In summary, loss of whisker inputs upregulates the functions of excitatory neurons and synapses as well as the areas and sites of receiving synaptic inputs in the barrel cortices. We subsequently studied the influence of loss of whisker inputs on the GABAergic inhibitory neurons and synapses in the barrel cortices.
The inhibitory units in the barrel cortex are downregulated after loss of whisker inputs
Inhibitory units in our study included GABAergic neurons and their output synapses in the barrel cortices. Inter-spike intervals and threshold potential were analyzed to indicate active intrinsic properties. Inhibitory synaptic transmission was evaluated by recording spontaneous inhibitory postsynaptic currents (sIPSC) on pyramidal neurons. The processes on GABAergic neurons were accounted from the images taken by a confocal microscope.
Figure 6C illustrates VGSC-mediated threshold potentials (Vts) at GABAergic neurons. Vts values for spikes 1 up to 5 are 33.1±0.91, 38.86±0.78, 40.1±0.89, 40.52±0.91 and 40.75±1.1 in the WT neurons (open symbols; n=15), and are 30.69±1.27, 34.15±1.26, 34.88±1.22, 36.23±1.72 and 36.88±1.56 in the controls (filled, n=16). Vts values for corresponding spikes are statistically higher in the WT neurons than the controls (p<0.01). Thus, loss of whisker inputs attenuates the active intrinsic properties of inhibitory neurons in the barrel cortices.
In whisker-trimmed mice versus controls, we analyzed the changes of excitatory and inhibitory neurons in the barrel cortices. After loss of whisker inputs for a week, the functions of excitatory neurons and synapses as well as the sites of receiving excitatory inputs are upregulated (Figures 2 and 5). On the other hand, the functions of GABAergic neurons and synapses as well as the processes of receiving synaptic inputs are downregulated (Figures 6 and 8). These changes elevate the activity levels of network neurons in the barrel cortices, which may prevent a loss of their functions due to idle whisker inputs and increase their sensitivity to sensory inputs, as well as be ready to attracting the innervations from other sensory cortices and/or peripheral nerves for the remained modalities during the cross-modal sensory plasticity [39–42].
In terms of physiological impacts for bidirectional changes in pyramidal neurons vs. GABAergic neurons from the barrel cortex after the loss of whisker inputs, the upregulation of excitatory units and the downregulation of inhibitory units will reset the balance of excitation versus inhibition toward the end of excitation. In addition to reducing the threshold to boost neuronal networks, this upregulated activity may maintain the sensitivity of pyramidal neurons to weak input, so that their functions are not lost. Moreover, their upregulated activities may attract the exogenous inputs to innervate the barrel cortices, such as from piriform cortex , for cross-modal sensory plasticity and rehabilitation. Upregulations in the frequency of excitatory synaptic events (Figure 3) and the sites of receiving synaptic inputs (Figures 4 and 5) grant the establishment of new excitatory innervations in the barrel cortices.
After a loss of whisker inputs, the capabilities of firing spikes and transmitting excitatory synaptic signals increase on pyramidal neurons in the barrel cortex (Figures 2 and 3). The capabilities of firing spikes on GABAergic cells and executing their synaptic outputs decrease (Figures 6 and 7). That is, the intrinsic property and synaptic transmission change coordinately for homogenous functions in experience-dependent neural plasticity. This coordinate change is also seen synaptic transmission and input structures, since excitatory synaptic events and dendritic spines increase in a loss of whisker inputs (Figures 3 and 5). The coordination in the neurons and synapses is critical for them to work in a common purpose, i.e., the increase of neuronal sensitivity to inputs boost the activity of neuronal networks for cross-modal sensory plasticity [41, 42]. In addition, we observed the bidirectional change between processes and their spines in apical and basal dendrites (Figures 4 and 5). This homeostasis in process density and spines saves the neuronal resources, a process similar to homeostasis by coordinating subcellular compartments and single molecules [43, 44]. Therefore, the coordination and homeostasis among the neurons and synapses are present in vivo, based on our studies, which expends this knowledge obtained from the studies in vitro.
In terms of the mechanism underlying the upregulation of excitatory units and the downregulation of inhibitory units after loss of sensory inputs in the barrel cortices, we assume that they use homeostatic mechanisms, which are seen in the studies in vitro. Neuronal activities undergo homeostatic upregulation after functional deficits by pharmacological or genetic manipulations [45, 46]. For instance, neuronal excitability rises when removing the treatment of TTX. The density of AMPA-type glutamate receptors is high when using CNQX. Neuronal excitability shows low and then recovery when potassium channels are over-expressed [47–49]. Such slowly developed homeostasis plays a role in functional compensation. The molecular mechanisms underlying neural homeostasis include glutamate/GABA receptors, voltage-gated sodium channels, brain-derived neurotrophic factors and α/β CaM-kinases [50–56]. It remains to be investigated how these molecules are coordinately initiated in vivo for the plasticity of the barrel cortices after loss of whisker inputs.
Excitatory synaptic transmission and dendritic spines increase on pyramidal neurons of the barrel cortex after loss of whisker inputs. As the strength of synaptic activities from the thalamus input deceases due to a lack of information from whisker-trigeminal ganglion-thalamus afferent pathway, these increased events and input-targeting units at excitatory synapses may be from cerebral cortices for other modalities, which is supported by our previous study . This point brings insight into the concept that the neurons are never to be the functional silent units under the physiological condition. After loss of excitatory synaptic inputs, the neurons call up through the homeostatic mechanism, attract synaptic inputs from other cortical areas and execute new functions, e.g., cross-modal plasticity for sensory compensation. How the substitution of other cortical inputs to thalamus inputs is temporally controlled by the molecular events remains to be studied.
Previous studies in the barrel cortices after trimming whiskers indicated the changes in synaptic transmission [25, 26], synaptic plasticity [27–30], dendritic reo rganization [31, 32], spine generation [33, 34] and zinc-containing neural circuit reorganization [35, 36]. These data indicate the important roles of synaptic plasticity and circuit rewire in experience-dependent neural plasticity. By labeling different neurons as well as studying their functions and morphology, we are able to see the coordination and homeostasis among the different types of neurons and synapses in the barrel cortices after experience-dependent neural plasticity. Our study brings new information for this subject.
In summary, we have investigated experience-dependent plasticity in the barrel cortices after loss of whisker inputs. The upregulation of excitatory neurons and synapses as well as the downregulation of inhibitory neurons and synapses are associated with the loss of sensory inputs. The upregulated activities of network neurons, after loss of their original sensory inputs, will prevent the loss of their functions and attract the inputs from other cortical areas and/or peripheral nerves for cross-modal compensation.
Methods and materials
The entire procedures were approved by Institutional Animal Care Unit Committee (IACUC) in the Administration Office of Laboratory Animals at Beijing China (B10831).
A mouse model of removing whisker stimulus
In order to analyze the activities of barrel cortical neurons and synapses relevant to the changes in whiskers’ experience in cell-specific manner, we need the mice whose cortical neurons are labeled by different markers. We cross-matched the mice from strains of C57(Thy1YFP)BL/6N (from He in IBP-CAS) and FVB-Tg(GADGFP)4570Swn/J (Jackson Lab, USA). Pyramidal neurons in C57 mice were genetically labeled by yellow fluorescent protein (YFP), in which the promoter was Thy1 on the upstream of YFP. GABAergic neurons in FVB mice were labeled by green fluorescent protein (GFP), in which the promoter was GAD on the upstream of GFP. Such cross-matched mice possess YFP-labeled pyramidal neurons and GFP-labeled GABAergic neurons in cerebral cortices (Figure 1). The mice in postnatal days 7 were divided into two groups that were whisker trimming on right side and control (intact whiskers), respectively. The whisker trimming was given every day for one week with no trimming the furs in the face of mice. During the operation, the mice were placed in home-made cages, in which their running and motion were restricted, but the extensions of their bodies and arms were allowed. The cares were taken including no stress and circadian disturbance to the mice. In addition, the mice with normal whisking and symmetric whiskers were selected for our experiments.
Brain slices and neurons
The cortical slices (400 μm) were prepared from the mice with whisker trimming and control. They were anesthetized by inhaling isoflurane and decapitated by guillotine. Slices were cut with a Vibratome in oxygenated (95% O2 and 5% CO2) artificial cerebrospinal fluid (ACSF), in which the concentrations (mM) of different elements were 124 NaCl, 3 KCl, 1.2 NaH2PO4, 26 NaHCO3, 0.5 CaCl2, 4 MgSO4, 10 dextrose, and 5 HEPES, pH 7.35 at 4°C. The slices were held in the oxygenated ACSF (124 NaCl, 3 KCl, 1.2 NaH2PO4, 26 NaHCO3, 2.4 CaCl2, 1.3 MgSO4, 10 dextrose, and 5 HEPES, pH 7.35) at 25°C for 2 hours. A slice was transferred to a submersion chamber (Warner RC-26G) that was perfused with the ACSF oxygenated at 31°C for whole-cell recording [41, 42, 57–60]. Chemical reagents were from Sigma.
The neurons in the barrel cortical slices are showed GFP-labeling for GABAergic cells and YFP-labeling for pyramidal cells. These neurons in layers II-III were selected for whole-cell recordings under DIC-fluorescent microscope (Nikon FN-E600, Japan), in which the excitation wavelength was 488 nm. GABAergic neurons showed fast spiking without the adaptation in spike amplitude and frequency, typical properties for interneurons [41, 61–64]. Cortical pyramidal neurons demonstrated regular spikes with the adaptation in their amplitudes and frequency.
Whole-cell recording and neuronal functions
Cortical neurons were recorded by an MultiClamp-700B amplifier under voltage-clamp for their synaptic activity and current-clamp for their active intrinsic properties. The electrical signals were inputted into pClamp-10 (Axon Instrument Inc, USA) for the data acquisition and analysis. The output bandwidth in this amplifier was 3 kHz. Pipette solution for studying excitatory events included (mM) 150 K-gluconate, 5 NaCl, 5 HEPES, 0.4 EGTA, 4 Mg-ATP, 0.5 Tris-GTP, and 5 phosphocreatine (pH 7.35; . The solution to record inhibitory synapses contained (mM) 130 K-gluconate, 20 KCl, 5 NaCl, 5 HEPES, 0.5 EGTA, 4 Mg-ATP, 0.5 Tris–GTP and 5 phosphocreatine . These pipette solutions were freshly made and filtered (0.1 μm). The osmolarity was 295~305 mOsmol and pipette resistance was 5~6 MΩ.
The functions of GABAergic neurons were assessed based on their active intrinsic properties and inhibitory outputs . The functional status of their inhibitory outputs were evaluated by recording spontaneous IPSCs (sIPSC) under voltage-clamp on pyramidal neurons in the presence of 10 μM 6-Cyano-7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX) and 40 μM D-amino-5-phosphonovanolenic acid (D-AP5) in ACSF to block ionotropic glutamate receptors and to isolate IPSCs . 10 μM bicuculline was washed into the slices at the end of experiments to test whether synaptic responses were mediated by GABAAR, which did block sIPSCs in our experiments. The series and input resistances for all of the neurons were monitored by injecting hyperpolarization pulses (5 mV/50 ms), and calculated by voltage pulses versus instantaneous and steady-state currents. It is noteworthy that the pipette solution with the high concentration of chloride ions makes the reversal potential to be −42 mV. sIPSCs are inward when the membrane holding potential at −65 mV .
The functions of pyramidal neurons were assessed based on their active intrinsic properties and excitatory outputs . The functional status of their excitatory outputs were evaluated by recording spontaneous EPSCs (sEPSC) under voltage-clamp on cortical pyramidal cells in presence of 10 μM bicuculline in ACSF to block ionotropic GABA receptors and isolate EPSCs. 10 μM CNQX and 40 μM DAP-5 were added into ACSF perfused into the slices at the end of experiments to test whether synaptic responses were mediated by GluR, which did block sEPSCs in our study. In addition, series and input resistances for all of these neurons were monitored by injecting hyperpolarization pulses (5 mV/50 ms), and calculated by voltage pulses vs. instantaneous and steady-state currents.
Action potentials at these cortical neurons were induced by injecting depolarization pulses, whose intensity and duration were changed based on the aim of experiments. The ability to convert excitatory inputs into sequential spikes was evaluated by inter-spike intervals (ISI) when depolarization pulses (200 ms in the duration and threshold for 10 ms pulse-induced spike for the intensity) were given . Neuronal intrinsic properties in our study included spike threshold potential (Vts) and absolute refractory period (ARP). Vts were the voltages of spike-onsets [43, 63, 69–71].
Data were analyzed if the recorded neurons had the resting membrane potentials negatively more than −60 mV, and action potential amplitudes more than 90 mV. The criteria for the acceptance of each experiment also included less than 5% changes in resting membrane potential, spike magnitude, and input resistance throughout each experiment. Input resistance was monitored by measuring cellular responses to hyperpolarization pulse at the same values as the depolarization that evoked action potentials. To estimate the effect of whisker trimming on neuronal spikes and synaptic transmission, we measured sEPSC, sIPSC ISI and Vts in the neurons from mice of control and whisker trimming. The differences in sEPSC, sIPSC, ISI and Vts were presented as mean±SE. The comparisons of these data were done by t-test.
The morphological studies of GABAergic neurons and pyramidal neuons in barrel cortices
The mice in one week after whisker trimming and controls were anesthetized by the intraperitoneal injection of sodium pentobarbital, and were perfused by 4% paraformaldehyde in 0.1 M phosphate buffer solution (PBS) from left ventricle/aorta until the body was rigid. The brains were quickly isolated and fixed in 4% paraformaldehyde PBS for additional 24 hours. Cortical tissues were sliced in the cross section of barrel cortex at 60 μm by a Vibratome. Sections were washed by PBS for 3 times, air-dried and cover-slipped. The images in the structures of YFP-labeled pyramidal neurons and GFP-GABAergic cells in the cross-sections of barrel cortices were photographed under a laser scanning confocal microscopy (Olympus FV-1000, Japan), in which their fluorescent markers were deconvoluted by 510 nm and 540 nm .
The structures of these neurons were analyzed by a commercialized software MetaMorph in Meta Imaging Series (ver. 6.1, Universal Imaging Cooperation in Molecular Device). As the brain tissues were sliced in series sections, the counting and analysis in cell structures were able to be done at least from two sections for each of barrels. The analyzed sections were chosen in a manner of one section from every two in order to prevent the influence of cells that crossed the neighboring sections on the analysis. In the analyses of dendrites, the primary processes (branches from somata) and secondary ones (branches from primaries) of pyramidal and GABAergic neurons were measured in each of barrel sections. In pyramidal neurons, the analyses of their dendrites included the apical and basal dendrites . The spines were the protrusion extended from on the dendrites, which were accounted as spines per 10 μm.
We thank Dr. SG He for C57(Thy1YFP)BL/6N mice. GJ Zhang and ZL Gao contribute to the experiments and data analyses. JH Wang contributes to project design and paper writing. This study is granted by National Basic Research Program (2013CB531304, 2011CB504405) and Natural Science Foundation China (30990261, 81171033) to JHW.
- Cruikshank SJ, Weinberger NM: Evidence for the Hebbian hypothesis in experience-dependent physiological plasticity of neocortex: a critical review. Brain Res Brain Res Rev 1996, 22:191–228.PubMedView Article
- Dulcis D, Spitzer NC: Reserve pool neuron transmitter respecification: Novel neuroplasticity. Dev Neurobiol 2011, 72:465–474.View Article
- Fox K: Experience-dependent plasticity mechanisms for neural rehabilitation in somatosensory cortex. Philos Trans R Soc Lond B Biol Sci 2009, 364:369–381.PubMedView Article
- Katz LC, Shatz CJ: Synaptic activity and the construction of cortical circuits. Science 1996, 274:1133–1138.PubMedView Article
- Kerr AL, Cheng SY, Jones TA: Experience-dependent neural plasticity in the adult damaged brain. J Commun Disord 2011, 44:538–548.PubMed
- Kleim JA, Jones TA: Principles of experience-dependent neural plasticity: implications for rehabilitation after brain damage. J Speech Lang Hear Res 2008, 51:S225-S239.PubMedView Article
- Leslie JH, Nedivi E: Activity-regulated genes as mediators of neural circuit plasticity. Prog Neurobiol 2011, 94:223–237.PubMedView Article
- Singer W: Development and plasticity of cortical processing architectures. Science 1995, 270:758–764.PubMedView Article
- Rogers LJ: The molecular neurobiology of early learning, development, and sensitive periods, with emphasis on the avian brain. Mol Neurobiol 1993, 7:161–187.PubMedView Article
- Foscarin S, Rossi F, Carulli D: Influence of the environment on adult CNS plasticity and repair. Cell Tissue Res 2012, 349:161–167.PubMedView Article
- Glasper ER, Schoenfeld TJ, Gould E: Adult neurogenesis: optimizing hippocampal function to suit the environment. Behav Brain Res 2011, 227:380–383.PubMedView Article
- Karmarkar UR, Dan Y: Experience-dependent plasticity in adult visual cortex. Neuron 2006, 52:577–585.PubMedView Article
- O'Leary DD, Ruff NL, Dyck RH: Development, critical period plasticity, and adult reorganizations of mammalian somatosensory systems. Curr Opin Neurobiol 1994, 4:535–544.PubMedView Article
- Shideler KK, Yan J: M1 muscarinic receptor for the development of auditory cortical function. Mol Brain 2010, 3:29.PubMedView Article
- Vida MD, Vingilis-Jaremko L, Butler BE, Gibson LC, Monteiro S: The reorganized brain: how treatment strategies for stroke and amblyopia can inform our knowledge of plasticity throughout the lifespan. Dev Psychobiol 2012, 54:357–368.PubMedView Article
- Byrne JH: Cellular analysis of associative learning. Physiol Rev 1987, 67:329–439.PubMed
- Descalzi G, Li XY, Chen T, Mercaldo V, Koga K, Zhuo M: Rapid synaptic potentiation within the anterior cingulate cortex mediates trace fear learning. Mol Brain 2012, 5:6.PubMedView Article
- Kandel ER: The molecular biology of memory: cAMP, PKA, CRE, CREB-1, CREB-2, and CPEB. Mol Brain 2012, 5:14.PubMedView Article
- Lansner A: Associative memory models: from the cell-assembly theory to biophysically detailed cortex simulations. Trends Neurosci 2009, 32:178–186.PubMedView Article
- Mayes A, Montaldi D, Migo E: Associative memory and the medial temporal lobes. Trends Cogn Sci 2007, 11:126–135.PubMedView Article
- Suzuki WA: Associative learning signals in the brain. Prog Brain Res 2008, 169:305–320.PubMedView Article
- Padamsey Z, Emptage NJ: Imaging synaptic plasticity. Mol Brain 2011, 4:36.PubMedView Article
- Pulvirenti L: Neural plasticity and memory: towards an integrated view. Funct Neurol 1992, 7:481–490.PubMed
- Holtmaat A, Svoboda K: Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 2009, 10:647–658.PubMedView Article
- Finnerty GT, Roberts LS, Connors BW: Sensory experience modifies the short-term dynamics of neocortical synapses. Nature 1999, 400:367–371.PubMedView Article
- Hardingham N, Wright N, Dachtler J, Fox K: Sensory deprivation unmasks a PKA-dependent synaptic plasticity mechanism that operates in parallel with CaMKII. Neuron 2008, 60:861–874.PubMedView Article
- Clem RL, Barth A: Pathway-specific trafficking of native AMPARs by in vivo experience. Neuron 2006, 49:663–670.PubMedView Article
- Jiao Y, Zhang C, Yanagawa Y, Sun QQ: Major effects of sensory experiences on the neocortical inhibitory circuits. J Neurosci 2006, 26:8691–8701.PubMedView Article
- Sun QQ, Zhang Z: Whisker experience modulates long-term depression in neocortical gamma-aminobutyric acidergic interneurons in barrel cortex. J Neurosci Res 2011, 89:73–85.PubMedView Article
- Wen JA, Barth AL: Input-specific critical periods for experience-dependent plasticity in layer 2/3 pyramidal neurons. J Neurosci 2011, 31:4456–4465.PubMedView Article
- Lendvai B, Stern EA, Chen B, Svoboda K: Experience-dependent plasticity of dendritic spines in the developing rat barrel cortex in vivo. Nature 2000, 404:876–881.PubMedView Article
- Rema V, Armstrong-James M, Ebner FF: Experience-dependent plasticity is impaired in adult rat barrel cortex after whiskers are unused in early postnatal life. J Neurosci 2003, 23:358–366.PubMed
- Holtmaat A, De Paola V, Wilbrecht L, Knott GW: Imaging of experience-dependent structural plasticity in the mouse neocortex in vivo. Behav Brain Res 2008, 192:20–25.PubMedView Article
- Vees AM, Micheva KD, Beaulieu C, Descarries L: Increased number and size of dendritic spines in ipsilateral barrel field cortex following unilateral whisker trimming in postnatal rat. J Comp Neurol 1998, 400:110–124.PubMedView Article
- Brown CE, Dyck RH: Experience-dependent regulation of synaptic zinc is impaired in the cortex of aged mice. Neuroscience 2003, 119:795–801.PubMedView Article
- Land PW, Shamalla-Hannah L: Experience-dependent plasticity of zinc-containing cortical circuits during a critical period of postnatal development. J Comp Neurol 2002, 447:43–56.PubMedView Article
- Sachdev RN, Egli M, Stonecypher M, Wiley RG, Ebner FF: Enhancement of cortical plasticity by behavioral training in acetylcholine-depleted adult rats. J Neurophysiol 2000, 84:1971–1981.PubMed
- Wallace H, Glazewski S, Liming K, Fox K: The role of cortical activity in experience-dependent potentiation and depression of sensory responses in rat barrel cortex. J Neurosci 2001, 21:3881–3894.PubMed
- Bavelier D, Neville HJ: Cross-modal plasticity: where and how? Nat Rev Neurosci 2002, 3:443–452.PubMed
- Lomber SG, Meredith MA, Kral A: Cross-modal plasticity in specific auditory cortices underlies visual compensations in the deaf. Nat Neurosci 2010, 13:1421–1427.PubMedView Article
- Ni H, et al.: Upregulation of barrel GABAergic neurons is associated with cross-modal plasticity in olfactory deficit. PLoS One 2010, 5:e13736.PubMedView Article
- Ye B, Huang L, Gao Z, Chen P, Ni H, Guan S, Zhu Y, Wang JH: The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs. PLoS One 2012, 7:e41986.PubMedView Article
- Chen N, Chen X, Wang J-H: Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding. Journal of Cell Science 2008, 121:2961–2971.PubMedView Article
- Ge R, Chen N, Wang JH: Real-time neuronal homeostasis by coordinating VGSC intrinsic properties. Biochem Biophys Res Commun 2009, 387:585–589.PubMedView Article
- Turrigiano GG, Nelson S: Homeostatic plasticity in the developing nervous system. Nat Rev Neurosci 2004, 5:97–107.PubMedView Article
- Burrone J, Murthy V: Synaptic gain control and homeostasis. Curr Opin Neurobiol 2003, 13:560–567.PubMedView Article
- Desai NS, Rutherford L, Turrigiano GG: Plasticity in the intrinsic excitability of cortical pyramidal neurons. Nat Neurosci 1999, 2:515–520.PubMedView Article
- Ramakers GJ, Corner MA, Habers AM: Development in the absence of spontaneous bioelectric activity results in increased stereotyped burst firing in cultures of associated cerebral cortex. Exp Brain Res 1990, 79:157–166.PubMedView Article
- Van Den Pol AN, Obrietan K, Belousov A: Glutamate hyperexcitability and seizure-like activity throughout the brain and spinal cord upon relief from chronic glutamate receptor blockade in culture. Neuroscience 1996, 74:653–674.PubMedView Article
- Burrone J, O'Byrne M, Murthy VN: Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons. Nature 2002, 420:414–418.PubMedView Article
- Desai NS, Rutherford LC, Turrigiano GG: BDNF regulates the intrinsic excitability of cortical neurons. Learn Mem 1999, 6:284–291.PubMed
- Demarque M, Spitzer NC: Neurotransmitter phenotype plasticity: an unexpected mechanism in the toolbox of network activity homeostasis. Dev Neurobiol 2011, 72:22–32.View Article
- Ehlers MD: Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat Neurosci 2003, 6:231–242.PubMedView Article
- Perez-Otano I, Ehlers MD: Homeostatic plasticity and NMDA receptor trafficking. Trends Neuroscie 2005, 28:229–238.View Article
- Spitzer NC, Borodinsky LN, Root CM: Homeostatic activity-dependent paradigm for neurotransmitter specification. Cell Calcium 2005, 37:417–423.PubMedView Article
- Thiagarajan TC, Piedras-Renteria ES, Tsien RW: Alpha- and beta-CaMKII. Inverse regulation by neuronal activity and opposing effects on synaptic strength. Neuron 2002, 36:1103–1114.PubMedView Article
- Wang J-H, Kelly PT: Ca2+/CaM signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal fast-spiking neurons of hippocampal CA1. J Physiol 2001, 533:407–422.PubMedView Article
- Yu J, Qian H, Chen N, Wang JH: Quantal glutamate release is essential for reliable neuronal encodings in cerebral networks. PLoS One 2011, 6:e25219.PubMedView Article
- Yu J, Qian H, Wang JH: Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes. Mol Brain 2012, 5:26.PubMedView Article
- Zhang F, Liu B, Lei Z, Wang J: mGluR1,5 activation improves network asynchrony and GABAergic synapse attenuation in the amygdala: implication for anxiety-like behavior in DBA/2 mice. Mol Brain 2012, 5:20.PubMedView Article
- Freund TF, Buzsaki G: Interneurons of the hippocampus. Hippocampus 1996, 6:347–470.PubMedView Article
- McKay BE, Turner RW: Physiological and morphological development of the rat cerebellar Purkinje cell. J Physiol 2005,567(Pt3):829–850.PubMedView Article
- Wang JH, Wei J, Chen X, Yu J, Chen N, Shi J: The gain and fidelity of transmission patterns at cortical excitatory unitary synapses improve spike encoding. J Cell Sci 2008, 121:2951–2960.PubMedView Article
- Wang Q, Liu X, Ge R, Guan S, Zhu Y, Wang JH: The postnatal development of intrinsic properties and spike encoding at cortical GABAergic neurons. Biochem Biophys Res Commun 2009, 378:706–710.PubMedView Article
- Ge R, Qian H, Wang JH: Physiological synaptic signals initiate sequential spikes at soma of cortical pyramidal neurons. Mol Brain 2011, 4:19.PubMedView Article
- Wei J, Zhang M, Zhu Y, Wang JH: Ca2+−calmodulin signalling pathway upregulates GABA synaptic transmission through cytoskeleton-mediated mechanisms. Neuroscience 2004, 127:637–647.PubMedView Article
- Wang J-H: Short-term cerebral ischemia causes the dysfunction of interneurons and more excitation of pyramidal neurons. Brain Res Bull 2003, 60:53–58.PubMedView Article
- Chen N, Zhu Y, Gao X, Guan S, Wang J-H: Sodium channel-mediated intrinsic mechanisms underlying the differences of spike programming among GABAergic neurons. Biochem Biophys Res Commun 2006, 346:281–287.PubMedView Article
- Chen N, Chen SL, Wu YL, Wang JH: The refractory periods and threshold potentials of sequential spikes measured by whole-cell recordings. Biochem Biophys Res Commun 2006, 340:151–157.PubMedView Article
- Chen N, Chen X, Yu J, Wang J-H: After-hyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels. Biochem Biophys Res Commun 2006, 346:938–945.PubMedView Article
- Chen N, Yu J, Qian H, Ge R, Wang JH: Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical pyramidal neurons. PLoS One 2010,5(7):e11868.PubMedView Article
- Zhao J, Wang D, Wang J-H: Barrel cortical neurons and astrocytes coordinately respond to an increased whisker stimulus frequency. Molecular Brain 2012,5(12):1–10.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.