The best method to distinguish between these two possibilities is to generate map plasticity

using a method that is independent of learning and then test the behavioral consequences. A finding that map plasticity has no effect on learning would suggest map plasticity is an epiphenomenon; the finding that map plasticity improves learning would indicate that map plasticity is indeed functionally relevant, even if unnecessary for continued task performance. Nucleus basalis stimulation (NBS) can be used to create cortical plasticity outside of a behavioral context. NBS during tone presentation leads to stimulus-specific map expansions in both primary and secondary auditory cortex (Bakin and LBH589 price Weinberger, 1996, Froemke et al., 2007, Kilgard and Merzenich, 1998 and Puckett et al., 2007). Plasticity has also been observed in the inferior colliculus and auditory thalamus after NBS-tone pairing, apparently due to the influence of cortical feedback connections onto these subcortical stations (Ma and Suga, 2003 and Zhang and Yan, 2008). Although nucleus

basalis is active during both aversive and appetitive behavioral tasks, NBS is motivationally neutral (Miasnikov et al., 2008). Previous studies have demonstrated that NBS-tone pairing causes map expansions that are similar to the plasticity Dorsomorphin seen after tone discrimination learning (Bakin and Weinberger, 1996, Bjordahl

et al., 1998 and Kilgard and Merzenich, 1998). NBS and tone exposure must occur within a few seconds of each other for stimulus-specific map plasticity to occur (Kilgard and Merzenich, 1998 and Metherate and Ashe, 1991). Passive exposure to tones without NBS does not result in map reorganization (Bakin and Weinberger, 1996, Bao et al., 2001 and Recanzone et al., 1993). In the current study, we used NBS paired with tones to determine the functional consequence of auditory cortex map plasticity. In the first experiment, we used NBS-tone pairing to cause auditory Ribonucleotide reductase cortex map expansions before discrimination learning. In the second experiment, we used NBS-tone pairing in animals that had already learned to perform the discrimination task. We performed neurophysiological recordings in all groups of animals to measure cortical map plasticity after NBS-tone pairing and behavioral training. For our study, it was important that the map expansions caused by NBS-tone pairing last long enough to evaluate the behavioral consequences of map plasticity. We have previously reported that 20 days of NBS-tone pairing results in map expansions in the primary auditory cortex (A1) that last at least 48 hr after the end of pairing (Kilgard and Merzenich, 1998).

Colocalization between nectin1 and nectin3 was observed at multiple locations within the cell bodies and distal

processes of CR cells (Figure S3C). Together, these data demonstrate that nectin1 and nectin3 are appropriately localized to mediate interactions between CR cells and migrating neurons. Because nectin3 preferentially forms heterotypic adhesions with nectin1 (Satoh-Horikawa et al., 2000), we next determined whether nectin1 expression in CR cells is required for the radial migration of nectin3-expressing neurons. For this purpose, we took advantage of our double-electroporation strategy (Figure 5A). We first electroporated hem-derived CR cells at E11.5 with a DN-nectin1 www.selleckchem.com/products/ABT-888.html construct that lacks the afadin binding site (Brakeman et al.,

2009 and Takahashi et al., 1999). The same embryos were re-electroporated at E13.5 with a Dcx-mCherry expression vector to label migrating neurons and then analyzed at E17.5. CR cells expressing DN-nectin1 still migrated along their normal route within the cortical MZ (Figures S4A–S4D). Quantitative evaluation confirmed that ∼50% of all reelin+ CR cells expressed DN-nectin1, even in the lateral cortex at a substantial selleck chemicals llc distance from the cortical hem (Figures 5C and 5D). These findings show that our electroporation method targets half of all CR cells and that DN-nectin1 does not significantly affect their tangential migration. However, the positions of radially migrating neurons were strikingly

altered after nectin1 perturbation in CR cells. Neurons in controls had migrated into the upper part of the CP, whereas large numbers of neurons remained in the lower part of the CP following expression of DN-nectin1 in CR cells (Figures 5E and 5F). Neurons in controls had normal bipolar morphologies with leading processes that branched in the MZ, whereas branch density was drastically decreased following expression of DN-nectin1 Parvulin in CR cells (Figures 5G and 5H). Similar defects in migration and leading-process arborization were found when nectin1 function in CR cells was perturbed using shRNAs (Figures S4E–S4I). Finally, nectin1 perturbation in CR cells did not produce obvious changes in the morphologies of RGC processes or the localization of RGC endfeet (Figure S4J). We conclude that perturbation of nectin1 function in CR cells affects interactions between neuronal leading processes and CR cells, thereby nonautonomously perturbing somal translocation of radially migrating neurons into the CP. We have previously shown that Cdh2 in neurons is required for glia-independent somal translocation (Franco et al., 2011); we now show that nectin3 and afadin in neurons are also required for this process. In epithelial cells, nectins form nascent cell-cell adhesion sites, to which afadin is recruited by binding to the cytoplasmic tails of nectins.

Type IIa fibers exhibit characteristics

learn more of both Type I and Type IIb fibers. They resemble Type IIb fibers in that they are large, fast, capable of forceful contraction, and high in glycolytic capacity. They are also similar to Type I fibers because they have more mitochondria, a moderate capillary supply, and higher oxidative capacity compared with Type IIb fibers. Type IIb fibers are the largest, fastest, and most forceful of the three main fiber categories. They have a low oxidative capacity, but high anaerobic glycolytic capacity and are capable of producing large amounts of lactic acid, fatiguing easily. Studies have shown that the skeletal muscle of obese adults are comprised of a lower proportion of oxidative type I skeletal muscle fibers muscle.37 and 38 This would suggest oxidative metabolism is attenuated in the obese and this proposition is supported by

evidence that obese adults show an impaired capacity to oxidize fats, which has been coupled to hastened weight gain.39 In children there has been no thorough investigation of the relationship HKI-272 nmr between adiposity and skeletal muscle fiber type, largely because of ethical limitations of the muscle biopsy. There is evidence that the young child is an “oxidative specialist”, possessing few Type IIb skeletal muscle fibers and a predominance of Type I and Type IIa skeletal muscle fibers.40 The percentage distribution of type IIa and IIb skeletal muscle fibers attains adult values during late adolescence.38 Whether the developmental trajectory toward the adult skeletal muscle fiber distribution pattern differs in the obese children is not known. There is limited evidence of impaired exercise fat oxidation in the obese children. Zunquin et al.41 reported lower maximal exercise fat oxidation values for obese pubertal boys compared

to the lean. Evidence is available that indicates deficits in fat oxidation can be reversed through targeted PA intervention, which may also augment positive alterations in body composition.42 and 43 It should be noted though, that these interventions these have all been delivered in combination with dietary manipulation and it is therefore not possible to ascertain the respective influence of the PA intervention or the dietary manipulation. Unlike adults, impaired fat oxidation has not been shown to predict future development of obesity in childhood.44 One explanation for deficits in skeletal muscle oxidative metabolism in the obese is that shifts in intracellular processes occur such as reductions in key enzymes associated with the oxidation of fats such as citrate synthase, thus reducing the capacity for fatty acid oxidation in skeletal muscle.45 These changes may be brought about simply by the changes in body composition associated with being obese, and are indeed more pronounced in the severely obese.45 Alternatively, they may be related to the combined effect of being obese and a lack of adequate muscular contraction.

When studied in vivo, blocking NMDA-Rs typically results in an increase in cortical gamma power, possibly due to a differential effect of blocking NMDA-Rs on a subset of inhibitory neurons (Carlén et al., 2011 and Korotkova et al., 2010). In contrast, most studies

performed in vitro report no effect of blocking NMDA-RS when oscillations are induced by adding cholinergic or glutamatergic agonists to the bath (Roopun et al., 2008). In the latter experiments, the added agonists may have provided the sustained depolarization necessary to maintain oscillations by acting through NMDAR-independent mechanisms, rendering NMDA-R blockade ineffective. Here, we show that persistent activity in CHIR-99021 order the avian OT depends on a circuit that utilizes NMDA-Rs. KU 55933 The circuit also generates gamma periodicity. However, the rhythmicity and the persistence represent two separable components of the circuit. In our experiments, pharmacological

agents were not required to produce oscillations. Hence, our results are consistent with studies that show a marked reduction in the duration of gamma oscillations resulting from NMDA-R blockade when such oscillations are induced in slices without pharmacological agents (Gandal et al., 2011). Long-lasting currents with kinetics similar to NMDA-R currents have been suggested to generate and maintain persistent activity in a variety of brain structures, both in vivo Florfenicol and in vitro (McCormick et al., 2003, Seung et al., 2000 and Wang, 1999) including in the OT/SC (Isa and Hall, 2009). However, no gamma oscillations were observed in previous in vitro studies that showed persistent activity in the OT/SC. Key differences from our study are that connectivity with cholinergic isthmic circuitry was probably not maintained and GABA-R antagonists were added to the bath to enhance network excitability (Isa and Hall, 2009 and Pratt et al., 2008). As in the forebrain (Bartos et al., 2007),

ionotropic GABA-R currents regulate the periodicity of gamma oscillations in the avian midbrain. Antagonizing GABA-Rs with PTX transformed gamma periodicity into bouts of persistent, high-frequency firing. Alternatively, enhancing GABA-R function with pentobarbital slowed the frequency of the oscillations. We also observed rhythmic IPSCs in the i/dOT that exhibited phase coherence with the LFP in the gamma band. In many mammalian forebrain structures, parvalbumin-positive interneurons are specifically implicated in the generation of gamma (Cardin et al., 2009 and Sohal et al., 2009). While the present study does not implicate a specific class of interneurons in gamma generation, immunostaining reveals a population of parvalbumin positive neurons that are clustered in layer 10a of the i/dOT (Figure 8A). ACh-Rs regulate the overall excitability of the midbrain oscillator. Blockade of AChRs reduces the duration and power of the oscillations without affecting their periodicity.

The large majority of mammals have two types of horizontal cells. Both of them feed back onto the rod or cone photoreceptors. Some rodents have click here only one type, and there have occasionally been proposals of a third type in some animals. Despite some variation in morphological detail, though, horizontal cells appear to follow a fairly simple

plan (Müller and Peichl, 1993; Peichl et al., 1998). Horizontal cells provide inhibitory feedback to rods and cones and possibly to the dendrites of bipolar cells, though this remains controversial (Herrmann et al., 2011). The leading interpretation of this function is that it provides a mechanism of local gain control to the retina. The horizontal cell, which has a moderately wide lateral spread and is coupled to its neighbors by gap junctions, measures the average level of illumination falling upon a region of the retinal surface. It then subtracts a proportionate value from Torin 1 in vitro the output of the photoreceptors. This serves to hold the signal input to the inner retinal circuitry within its operating range,

an extremely useful function in a natural world where any scene may contain individual objects with brightness that varies across several orders of magnitude. The signal representing the brightest objects would otherwise dazzle the retina at those locations, just as a bright object in a dim room saturates a camera’s film or chip, making it impossible to photograph the bright object at the same time as the dimmer ones. Because the horizontal cells are widely spreading cells,

their feedback signal spatially overshoots the edges of a bright object. This means that objects neighboring a bright object have their signal reduced as well; in the extreme, the area just about outside a white object on a black field is made to be blacker than black. This creates edge enhancement and is part of the famous “center-surround” organization described in classic visual physiology (Hartline, 1938; Kuffler, 1953). But the inner retina contains many more lateral pathways than the outer, and creates both simple and sophisticated contextual effects. Indeed, Peichl and González-Soriano (1994) pointed out that the ganglion cells of mice and rats have a quite ordinary center-surround organization, but these retinas lack one type of horizontal cell altogether. Perhaps the horizontal cells are best imagined as carrying out a step of signal conditioning, which globally adjusts the signal for reception by the inner retina, rather than being tasked primarily with the detection of edges. The synapses by which horizontal cells provide their feedback signals appear to use both conventional and unconventional mechanisms; they remain a matter of active investigation (Hirano et al., 2005; Jackman et al., 2011; Klaassen et al., 2011). Taken as morphological populations, however, the horizontal cells are relatively simple. They can be stained for a variety of marker proteins in different animals.

The six seed ROIs selected for this analysis were defined in the left hemisphere according to anatomical criteria (see Experimental Procedures; see also Figure S1 and

Table S1 available online) and included the lateral prefrontal cortex (LPFC), posterior part of inferior frontal gyrus (IFG), “hand knob” area of central sulcus (CS), anterior intraparietal sulcus (aIPS), posterior part of superior temporal gyrus (STG), and lateral occipital sulcus (LO). Selecting right hemisphere ROIs would have yielded a complementary analysis with equivalent findings. Strong correlations with the seed time course were found in voxels adjacent to the location of the seed (white ellipses, Dasatinib solubility dmso Figure 1) and in voxels located in the homologous

area of selleck chemicals the contralateral right hemisphere. Note two important points. First, the voxels that exhibited correlation with each seed showed high spatial selectivity with very little overlap across seeds: this means that the spontaneous activity found for each seed and its corresponding contralateral location was relatively unique and different from that found for each of the other seeds and their contralateral locations. Second, the strength and spread of correlation in the contralateral locations are qualitatively similar across groups in all areas except for STG and IFG, which appear abnormally reduced in the autism group. Voxel-by-voxel comparisons showed that toddlers with autism exhibited significantly weaker interhemispheric correlations than both typically developing and language-delayed toddlers in the STG, a cortical area commonly associated with language processing (Figure 2). The comparisons of the Dichloromethane dehalogenase autism group to each of the other groups were independent of one another, yet both revealed significant synchronization differences only in voxels located within the STG. This analysis was performed by first computing the correlation between the time course of each left-hemisphere voxel and the time course of its corresponding contralateral right-hemisphere

voxel in each subject. This gave us an interhemispheric correlation value for each pair of corresponding left/right voxels, which signified their synchronization strength. We then performed a t test for each voxel, contrasting the correlation values across individuals of different groups. This analysis yields symmetrical results across the two hemispheres, hence the presentation of the voxel-wise group differences only on the left hemisphere. Presenting the results on the right hemisphere yields a reciprocal “mirror image. The results found in STG raised the possibility that poor interhemispheric synchronization may be a characteristic of the language system in toddlers with autism. To evaluate this further, we performed an ROI analysis in six anatomically defined ROIs that included two putative language areas, STG and IFG, and four control areas, LO, aIPS, CS, and LPFC.

Pairwise comparisons within multiple

groups were done by ANOVA followed by the Fisher’s PLSD post hoc test. Data are presented as the mean + SEM. ∗∗∗∗p < 0.001; ∗∗∗p < 0.005; ∗∗p < 0.01; ∗p < 0.05; NS, not significant. Asterisks in the figures denote t test comparisons between experimental group and control in each experiment. We thank the members of Dabrafenib price the Bonni laboratory for helpful discussions and critical reading of the manuscript. This work was supported by NIH grants NS041021 (A.B.), GM054137 (J.W.H), and AG011085 (J.W.H). “
“Neurotransmission relies on the fusion of synaptic vesicles (SVs) with the plasma membrane at the presynaptic terminals, where SVs are clustered near the active zones (AZs). AZs are specialized regions of the plasma membrane defined by a protein meshwork that contains the molecular machinery necessary for SV recruitment and recycling (Jin and Garner, 2008; Owald and Sigrist, 2009; Südhof, 2012). The number, size, and location of synapses vary among different types of neurons and critically impact the efficacy of neurotransmission

(Atwood and Karunanithi, 2002; Holderith et al., 2012). For example, in both vertebrate and invertebrate nervous systems, some neurons specify a single synaptic connection at the axon terminal, while others elaborate sequential release sites called en passant synapses. Although many extrinsic cues and cell surface molecules have been shown to shape synaptic connectivity (Shen and Scheiffele, selleck screening library 2010), our understanding of the intracellular mechanisms involved in synaptic patterning remains incomplete. The targeting of SVs and AZ proteins to specific sites Sitaxentan depends on their directed axonal delivery by molecular motors (Goldstein et al., 2008; Hirokawa et al., 2010). Electron and light micrographic studies have demonstrated that many SV components are trafficked in SV protein transport vesicles (STVs) (Matteoli et al., 1992; Ahmari et al., 2000; Tao-Cheng,

2007). Live imaging has revealed that STV packets travel along axons bidirectionally and intermittently, occasionally splitting into smaller packets or merging into larger clusters (Kraszewski et al., 1995; Dai and Peng, 1996; Ahmari et al., 2000; Sabo et al., 2006). In addition, they can rapidly accumulate at new axodendritic contact sites and become capable of stimulation-evoked SV recycling (Ahmari et al., 2000; Washbourne et al., 2002; Sabo et al., 2006). On the other hand, the 80-nm-dense core Piccolo-Bassoon transport vesicles (PTVs) are proposed to represent modular packets that assemble the AZ cytomatrix in vertebrate neurons (Zhai et al., 2001; Shapira et al., 2003; Maas et al., 2012). Interestingly, recent electron micrographic (EM) and live-imaging studies reported that AZ and SV proteins may be preassembled into multivesicle transport complexes and cotrafficked in cultured neurons (Tao-Cheng, 2007; Bury and Sabo, 2011).

Incomplete penetrance of ventral remodeling in double mutants

was also observed by imaging. In unc-55; hbl-1 double mutants, we observed patches of the ventral nerve cord that contained an approximately normal number of synapses, while other regions totally lacked synapses (data not shown). A transgene expressing hbl-1 in the VD and DD neurons of unc-55; hbl-1 double mutants (using the unc-25 promoter) decreased the ventral IPSC rate to that observed in unc-55 single mutants ( Figure 3F) but did not rescue the non-neuronal hbl-1 defects ( Figure S3A). These results suggest that HBL-1 acts in VD neurons to promote ectopic remodeling. To further document the functional integrity of the ventral VD synapses, we analyzed the locomotion behavior of unc-55; hbl-1 double mutants. A prior study showed that ectopic remodeling of VD synapses in unc-55 mutants was accompanied by a locomotion defect ( Zhou and Walthall, 1998). During backward Venetoclax movement, unc-55 mutants assume a ventrally coiled body posture, presumably due to the absence of inhibitory input to the ventral body muscles ( Figure 3I). This unc-55 coiling defect was significantly reduced (but not eliminated) in unc-55; hbl-1 double mutants ( Figure 3I). The coiling defect was restored by transgenes driving hbl-1 expression in the D neurons (using either the unc-25 GAD or the unc-30 promoter) in unc-55; hbl-1 double mutants ( Figure 3I and Figure S3E),

as would be predicted if HBL-1 acts in VD neurons to this website promote remodeling. Thus,

the imaging, electrophysiology, and behavioral assays all support the idea that hbl-1 is a functionally important UNC-55 target whose expression promotes ectopic remodeling of VD synapses in unc-55 mutants. The partial suppression and incomplete penetrance observed in the unc-55; hbl-1 double during mutants indicate that the hbl-1(mg285) mutation did not completely abolish remodeling of VD synapses. The persistent VD remodeling observed in double mutants could reflect residual hbl-1 activity in hbl-1(mg285) mutants, or the activity of other UNC-55 target genes ( Lin et al., 2003). Consistent with the latter idea, transgenic expression of hbl-1 in DD and VD neurons (with the unc-25 promoter) was not sufficient to cause ectopic remodeling of VD synapses ( Figure S3F). Thus, hbl-1 is unlikely to be the only UNC-55 target involved in D neuron remodeling. Thus far, our results show that hbl-1 promotes ectopic remodeling of unc-55 mutant VD neurons but that hbl-1 expression alone is not sufficient to cause VD remodeling. We next analyzed DD remodeling, which occurs in wild-type animals ( Walthall, 1990 and White et al., 1978). Prior to hatching, DD neurons form ventral NMJs, which can be identified as ventral UNC-57::GFP puncta. During the L1 stage, these ventral DD synapses are eliminated and new dorsal synapses are formed (visualized as dorsal UNC-57 or RAB-3 puncta; Figure 4A and Figure S4A).

, 2007). Therefore, it was important to determine

the effect of zinc on heteromeric GluK2/GluK3 receptors. To test the specific effects of zinc on GluK2/GluK3 heteromers in cells cotransfected with GluK2 Vorinostat and GluK3, we reduced the likeliness of activating homomeric GluK2 or GluK3 subunits as described previously ( Perrais et al., 2009b). First, the GluK2b(Q) splice variant was used because of its reduced expression at the cell surface as a homomer ( Jaskolski et al., 2004). Second, GluK3 homomeric receptors were specifically blocked with 1 μM UBP310 ( Perrais et al., 2009b). In cells cotransfected with GluK2b(Q) and GluK3, application of 1 μM UBP310 inhibited glutamate-activated currents by 55% (n = 6; p < 0.05). The fraction of current resistant to UBP310 was enhanced by zinc (100 μM) to a similar extent (157% ± 7%, n = 18) as for homomeric GluK3 receptors (p = 0.65; Figures 1B and 1C). The small fraction of homomeric GluK2 receptors at the cell surface would, if anything, find more lead to an underestimation of the potentiation of GluK2/GluK3 receptors by zinc. Therefore, these results clearly demonstrate that heteromeric GluK2/GluK3 receptors

are, like GluK3 receptors, potentiated by zinc. The modulation of GluK3 by zinc showed a dose-dependent biphasic effect: increasing the concentration of zinc up to 100 μM potentiated currents (half-maximal effect around 20 μM), and higher concentrations MycoClean Mycoplasma Removal Kit progressively inhibited currents (Figure 1D). In order to fit the dose-response

curve with combined potentiation/inhibition Hill equations, we hypothesized that the inhibition of GluK3 by higher concentrations of zinc was similar to that of GluK2 (a notion supported by the effects of point mutations described in Figure 6). This attempt to separate potentiation and inhibition in the GluK3 dose-response curves yielded an EC50 value of 46 ± 17 μM, nH 1.82 ± 0.95, and a maximal potentiation of 475% ± 47%, although the moderate quality of the combined fit suggests that potentiation and inhibition might not be independent processes. Surprisingly, zinc potentiated currents mediated by GluK2/GluK3 at all concentrations tested (Figure 1D), with an EC50 of 477 ± 1638 μM, nH 0.6 ± 0.4, consistent with a reduced number of binding sites on heteromeric receptors, and a maximal potentiation of 286% ± 195% of control, and by contrast to homomeric GluK3 receptors, there was no inhibition for zinc concentrations up to 1 mM. Zinc could affect GluK3-mediated currents in several ways: it could increase single-channel conductance, increase open probability, allow activation of “silent” receptors, or slow down receptor desensitization. It was shown previously that the low glutamate sensitivity of GluK3 receptors was due to fast transitions of glutamate bound receptors to desensitized states (Perrais et al.

External tufted cells exert this control at a fast timescale via chemical and electrical synapses. In contrast, we demonstrate here Ion Channel Ligand Library a mechanism by which external tufted cells regulate glomerular output at a much longer timescale. CTGF responsiveness is reminiscent of two other immediate-early genes, c-fos and Egr1 (also

known as Zif268 protein). Expression of c-fos and Egr1 in the glomerular layer already significantly increases 45 min after odor exposure ( Johnson et al., 1995). This regulation contrasts with the activity-dependent regulation of tyrosine hydroxylase (TH) in periglomerular neurons that decreases significantly only after several days following sensory deprivation ( Baker et al., 1993), again highlighting the diversity of temporal regulations that take place in glomeruli. In summary, we here identified CTGF as a proapoptotic factor whose activity-dependent increase of expression eliminated newborn neurons in a locally restricted manner. Our experiments showed that even a small increase in the number of surviving cells dramatically changed olfactory behavior. Survival/death choice is regulated by external stimuli, and the number of surviving cells is “adapted” according to the animal’s local environment. Since olfaction is the most important sensory mode for many mammals, “olfactory competition” for food, mating, and predator versus prey relationship plays

a decisive role during the life of an animal. Hence tight regulation of newly added neurons is a crucial mechanism enabling Phosphoprotein phosphatase an adaptive response to environmental changes. All antibodies and High Content Screening chemicals are listed in the Supplemental Experimental Procedures. All animal procedures were performed according to the regulations of Heidelberg University/German Cancer Research Center or Pasteur Institute

Animal Care Committees. To obtain miRNA cassettes expressed under the synapsin or GFAP promoter, we used the BLOCK-iT PolII system (Invitrogen, Germany) and subcloned miRNA cassettes to viral vectors containing the synapsin or GFAP promoter, respectively. shRNA constructs were cloned as previously described (Khodosevich et al., 2009). For details of cloning, see the Supplemental Experimental Procedures. The efficiency of mi/shRNA silencing was tested as previously described (Khodosevich et al., 2009). For details, see the Supplemental Experimental Procedures. Recombinant retroviruses and AAVs were produced as previously described (Khodosevich et al., 2009 and Khodosevich et al., 2012). The titer of the injected virus had been adjusted such as to be equal for all experiments—4 × 108 units/ml for AAVs and 108 units/ml for retroviruses. For double SVZ/OB injections, mice were first injected into the OB using glass capillary and immediately after into the SVZ by a Hamilton syringe (Hamilton, Switzerland). Injection procedure is described in the Supplemental Experimental Procedures.