Dynorphin expression is increased during periods of dehydration

and so continues to provide a feedback inhibition even while spike frequency is increased to counter dehydration effects by increasing vasopressin release (Scott et al., 2009). Dynorphin also reduces transmitter release from presynaptic glutamate axons (Iremonger and Bains, 2009). The dual effect of direct inhibition of release from the parent cell or its similar neighbors, and presynaptic reduction in excitatory transmitter stimulation, serve a similar role allowing dynorphin to depress activity by multiple converging mechanisms. Actions of dynorphin in attenuating hippocampal mossy fiber glutamate release are discussed above. Kisspeptin is synthesized by cells of the medial hypothalamus, and the peptide modulates the activity of GnRH neurons and regulates Ipatasertib molecular weight reproduction and onset of puberty (Kauffman et al., 2007; Han et al., 2005). Mutations of the GPR54, the kisspeptin receptor, block puberty and cause infertility in rodents and humans (Dungan et al., 2006; Smith and Clarke, 2007). Dynorphin and neurokinin B colocalize with kisspeptin in many mammals (Goodman et al., 2007); dynorphin is proposed to act back on the releasing kisspeptin neurons to synchronize and shape

pulsatile release patterns of kisspeptin (Navarro et al., 2009; Wakabayashi et al., 2010). Although we generally selleck inhibitor think of neuroactive peptides as being synthesized by and exerting effects on neurons, the focus of this review, glial cells may also employ neuropeptide signaling and express receptors for neuromodulators in the CNS (Azmitia et al., 1996; Kimelberg, 1988; Tasker et al., 2012). For instance, one class of olfactory ensheathing glia that accompanies

the olfactory nerve from the olfactory mucosa into the olfactory bulb shows very high levels of NPY expression (Ubink et al., 1994; Ubink and Hökfelt, 2000); NPY may act here as a trophic factor to promote olfactory receptor neuron maturation and survival (Doyle et al., 2012). Schwann cell precursors also express NPY, and this expression GPX6 is lost during postnatal development (Ubink and Hökfelt, 2000). NPY may also be released by astrocytes. Ramamoorthy and Whim (2008) employed NPY-bound red fluorescent protein to show glutamate-agonist mediated NPY secretion from cortical astrocytes. Astrocytes in many brain regions express functionally active vasopressin receptors (Brinton et al., 1998; Jurzak et al., 1995; Kozniewska and Romaniuk, 2008). Peptide-responsive astrocytes can show fairly rapid activity-dependent structural plasticity which may allow a further dimension of modulation of neuropeptide actions and diffusion (Miyata et al., 2001; Theodosis et al., 2008), including potential selective restriction of peptide diffusion from a release site.

For the three morphed images, M1, M2, and M3, there was a significantly higher activation when the subjects recognized the ambiguous images as person B (responsive) compared to A (nonresponsive) (Figure 3A). Moreover, the response to the three morphed images perceived as picture B did not differ statistically from the one obtained in response to the presentation of picture B without morphing. Similarly, the presentation of picture A (without morphing) elicited a response that did not differ statistically selleck compound from the one elicited by the morphed images when recognized as A. Figure 3B shows

the results pooled together the three morphs used. As before, there was a significantly larger response to picture B and the ambiguous pictures recognized as B, compared to picture A and the ambiguous pictures recognized as A. For each response (A or B) there were no significant differences in the neurons’ firing to the ambiguous and the original (nonmorphed) pictures. These results were consistent across MTL areas. That means, when considering the neurons of each area separately (hippocampus, amygdala, entorhinal cortex, and parahippocampal cortex), in all cases the response to the ambiguous pictures recognized as picture B were significantly larger than when recognized as A, and there were no significant

differences in the responses to the original (nonmorphed) pictures A or B and the ambiguous pictures recognized as picture A or B, respectively. This lack of significant differences between the ambiguous and the original pictures should, however, be interpreted selleck chemicals llc with caution, given that such null result could be due to an insufficient number of trials or a large variability in the responses across different neurons, among other factors. To further study this issue, we used a linear classifier to predict the presentation of the original or the ambiguous pictures leading to the same perceptual outcome (recognized A or recognized ALOX15 B). As before, we considered those responses for which we had at least five trials in each condition. In 10 out of 52 cases

(19%) the linear classifier could discriminate better than chance (p < 0.05) the presentation of the original picture B from the ambiguous picture recognized as B, whereas in 15 out of 62 cases (24%) the classifier could significantly distinguish between picture A and the ambiguous picture recognized as A. Complementing these results, in Figure 4 we show the time course of the normalized average instantaneous firing rate curves (see Experimental Procedures) for the four conditions (pictures A or B, and ambiguous pictures recognized as A or B). Note the similarity of the firing rate curves in response to the pure picture B and to the ambiguous pictures recognized as B (difference nonsignificant; Kolmogorov-Smirnov test).

However, rate code alone may not be able to accurately encode nonspatial features due to its coarseness: the fact that the firing rate is not homogenous inside the place field but increases toward its center causes ambiguities in the code. Let us assume that high peak-firing in the place field represents nonspatial feature A,

whereas reduced peak-firing in the same location reflects feature B. When that cell fires at the reduced rate, we might assume that it is signaling feature B. However, the same low rate can also occur in the presence of feature A, provided that the animal is only in the periphery of its place field (where rate is lower than at the peak by default). Theta phase precession enables a form of temporal code that can disambiguate this. The timing of a cell’s spike relative to the theta rhythm holds information

about the relative location of the animal within its place field: as the animal passes Selleckchem GSK2118436 through the field, spike timing gradually shifts to earlier theta phases (O’Keefe and Recce, 1993). In one-dimensional mazes, where this phenomenon was first observed, theta phase is directly related to the animal’s location. In this condition, theta phase precession has been suggested to provide a temporal BIBW2992 code for place, allowing firing rate to encode additional nonspatial features (Huxter et al., 2003). Theta phase precession is also present in 2D environments, where theta phase can identify whether cells fire at the center or the periphery of their place fields (Huxter et al., 2008). To return to our example, the theta spike timing can code whether the animal is at the center or at the periphery of the place field, and can therefore discriminate which nonspatial feature was present. Thus, a theta-based temporal code may be required to reliably decode the rate remapping code for nonspatial information. Rennó-Costa et al.

highlight important roles for feedback inhibition and gamma oscillatory control in rate remapping. Gamma Endonuclease oscillations are thought to reflect rhythmic inhibition and have been suggested to occur during memory acquisition or recall periods (Colgin et al., 2009). Therefore, the encoding of nonspatial mnemonic features by the rate modulation of place cells might be expected to take place preferentially during gamma oscillations. Moreover, gamma epochs often occur superimposed on theta oscillations, and at the same theta phase at which many place cells tend to fire at their highest rate (Senior et al., 2008). As a result, place cells that fire together during theta-modulated gamma oscillations may encode together nonspatial features of the environment. Under this scenario, which is also suggested by the model, only one cell assembly that encodes nonspatial features can escape from gamma-related feedback inhibition at a time.

At 4 days postinfection, the cells were harvested for

the luciferase assay and an LDH assay after OGD. Primary cortical neurons were infected with the purified adenovirus (adeno-CRE-Luc buy Ipatasertib [firefly] and adeno-TK-Luc [renilla]). The adenovirus containing a CMV promoter driving renilla luciferase was used as an internal control (Promega) as previously described (Katoh et al., 2006). Primary cortical neurons were fixed immediately with 4% PFA for 30 min. For double-immunofluorescence in vivo, free-floating sections (40 μm) were used. See Supplemental Experimental Procedures for details. To prepare an SIK2-Thr484 peptide, a set of oligonucleotides for the SIK2 peptide (Gly479 to Thr489: 5′-gatcGGGCAGCGACGGCACACTCTGTCAGAAGTGACT

Y-27632 nmr and 5′-aattAGTCACTTCTGACAGAGTGTGCCGTCGCTGCCC) was cloned into the BamHI/EcoRI site of the Escherichia coli GST-fusion vector pGEX6P-1, and the GST-SIK2 (Thr484) peptide was purified by using a glutathione-Sepharose column. To prepare active CaMKs, cDNA fragments for constitutive active CaMKs were ligated into the BamH1/NotI site of pEBG mammalian GST-fusion vector, and the active CaMKs were expressed in COS-7 cells followed by purification with a glutathione-Sepharose column. The GST-SIK2 (Thr484) peptide (1 μg) was incubated with CaMKs in a reaction buffer (10 mM Tris-HCl [pH 7.4], 10 mM MgCl2, in the presence or absence of 100 μM ATP) at room temperature for 1 hr, and phospho-SIK2 (Thr484) was detected by western blot analyses with anti-phospho-Thr484 antiserum. These were performed as previously described (Katoh et al., 2006) (see Supplemental Experimental Procedures). Data are representative of at least four independent experiments. Total RNA was extracted by using TRIzol (Invitrogen). cDNAs were prepared by reverse transcription (RT) from total RNA (1 μg) by using SuperScript III and random primers (Invitrogen). One-hundredth of the RT products and standard plasmids were subjected to real-time PCR analyses

with the iQ SYBR Green Supermix (Invitrogen) or TaqMan Probe Universal PCR Master Mix (Applied Biosystems). The specific primers used are listed in Table S1. See oxyclozanide Supplemental Experimental Procedures for details. The generation of Sik2+/− mice has been described by Horike et al. (2010); these mice are now supplied by JCRB Laboratory Animal Resource Bank at the National Institute of Biomedical Innovation (NIBIO) No. nbio071; http://animal.nibio.go.jp/index.html. Although Sik2+/− ES cells were established in C57BL/6-derived cells (RENKA), Sik2+/− mice were mated with C57BL/6J mice for ten generations; then, mouse colonies were amplified for the experiments. The experimental protocols using mice were approved by committees at the NIBO.