By contrast, when the same progenitor resumes proliferation in early larvae, it yields multiple identical neurons before transiting to produce a different neuron type. Strikingly, distinct adPN types show different reproducible cell counts (Yu et al., 2010). This stereotyped developmental blueprint clearly indicates that the neuronal birth order strictly dictates the fate of each neuron made through about 80 rounds of NB self-renewal.

What molecular mechanisms may specify so many neuron types with such fine temporal precision? The transcriptional cascade of Hunchback (Hb), Kruppel (Kr), POU domain proteins 1 and 2 (Pdm), and Castor (Cas) is known to specify the first several neurons across NB lineages in the embryonic ventral ganglion (for reviews, see Pearson and Doe, 2004 and Jacob et al., 2008). The

same transcriptional cascade or its variants may reiterate to specify additional neuron check details fates at later time points. Further, a single temporal factor may trigger discrete feedforward regulatory networks in the contiguously derived siblings to diversify neuron fates (Baumgardt et al., 2007 and Baumgardt et al., 2009). Although their involvement in the Drosophila central brain remains elusive, the Chinmo BTB-zinc finger nuclear protein was recently found to govern neuronal temporal identity in MB lineages via a different mechanism ( Zhu et al., 2006). Chinmo proteins exist among the sequentially derived MB neurons in a high-to-low temporal gradient that dictates

multiple MB temporal Bioactive Compound Library solubility dmso fates based during on the levels of Chinmo expression. The temporal gradient of Chinmo is established via a 5′ untranslated region (5′ UTR)-dependent translational control, and one can reproducibly elicit MB temporal cell-fate transformation in either direction by modulating Chinmo expression in newborn neurons. Determining Chinmo’s role(s) in additional neural lineages has revealed that it may govern neuronal temporal identity in lineage-specific manners. In a serial production of six distinct central complex neurons, Chinmo is specifically required in the third sibling for not adopting the fourth temporal cell fate ( Yu et al., 2009). And our earlier analysis of Chinmo function in the adPN lineage had been limited to the first larval-born adPN type, which was uniformly transformed to the fourth larval-born adPN type in the absence of Chinmo ( Zhu et al., 2006). To elucidate how numerous temporal fates could be invariably specified through a protracted neuronal lineage, we determined the role of known temporal fating factors, including Chinmo and the Hb/Kr/Pdm/Cas transcriptional cascade, in the serial production of 40 adPN types. We found that Chinmo governs neuronal temporal identity in two separate windows of adPN production. Chinmo acts to suppress the next Chinmo-independent temporal fate among all neurons born within each Chinmo-dependent window.

, 2011). Binding of the RIM zinc-finger to the Munc13 C2A domain disrupts the homodimers, thereby activating Munc13. As a result, RIM-deficient synapses exhibit a severe impairment in vesicle priming that can be click here rescued not only by the N-terminal RIM fragment, but also by expression of mutant Munc13 that is constitutively

monomeric, illustrating that the function of RIMs in priming consists of activating Munc13 (Deng et al., 2011). In addition to the regulation of the Munc13 MUN domain by RIMs, the MUN domain is controlled by the central signaling domains of Munc13 that comprise a calmodulin-binding sequence and the C1 and C2B domains (Figure 2) and that perform essential functions in regulating release (Rhee et al., 2002; Junge et al., 2004; Shin et al., 2010; see discussion below). It is unknown, however, whether the N-terminal sequences of bMunc13-2 and Munc13-3 have a regulatory role since they do not bind to RIMs, and no function has been observed yet for the conserved C2C domain of Munc13s. Addressing these questions may have general implications not only for synaptic exocytosis, I-BET151 research buy but also for other forms of exocytosis,

for example cytotoxic granule exocytosis in NK cells which requires Munc13-4 (Feldmann et al., 2003). α- and β-liprins are related proteins composed of an N-terminal half with a predicted coiled-coil domain, and three ADAMTS5 C-terminal SAM domains (Serra-Pagès et al., 1995). Two highly conserved sequence motifs in the N-terminal coiled-coil region are referred to as “liprin homology domains” LH1 and LH2 (Taru and Jin, 2011). The N-terminal half of α-liprins binds to itself to form homodimers (Taru and Jin, 2011), to the RIM

C2B domain (Schoch et al., 2002), to ELKS (Ko et al., 2003a and Dai et al., 2006), to mDiaphanous, a rho effector protein (Sakamoto et al., 2012), and to GIT1 (Ko et al., 2003b). The C-terminal SAM-domains, in turn, bind to β-liprins to form heterodimers (Serra-Pagès et al., 1995), to CASK (Olsen et al., 2005), and to LAR-type receptor phosphotyrosine phosphatases (PTPRF, PTPRD, and PTPRS; Serra-Pagès et al., 1995). Of these interactions, α-liprin binding to β-liprins, to receptor phosphotyrosine phosphatases, to ELKS, and to itself have been functionally validated (Kaufmann et al., 2002, Ackley et al., 2005, Dai et al., 2006, Taru and Jin, 2011 and Astigarraga et al., 2010). α-Liprins were first linked to presynaptic active zones when a loss-of-function mutation in C. elegans α-liprin was found to apparently increase the size of the active zone and to disrupt synaptic vesicle accumulation ( Zhen and Jin, 1999 and Dai et al., 2006), a finding that was confirmed in Drosophila ( Kaufmann et al., 2002). No studies on α-liprin function in vertebrate presynaptic terminals exist, but a rich body of work in C.

Survivors who participated in exercise had significant

improvements across a variety of domains. Improvements were seen in commonly used clinical outcome measures such as 6 minute walk test, handgrip strength, and SF36. Although 65% of the meta-analyses reviewed focused on breast cancer, Fong et al provide evidence that physical activity is beneficial across a variety of tumour streams after completion of treatment. However, cancer patients can also benefit from physical activity during treatment for their cancer (Knols et al 2005). Patients often Bortezomib cost have greater access to allied health services such as physiotherapy during active treatment compared to post treatment. Additionally, there is not always a clear

point in time when treatment is completed. Ideally BMS-387032 mw physiotherapists should establish an appropriate exercise program whilst the patient is undergoing active treatment, with a plan in place for ongoing exercise post treatment. Fong et al found that incorporating resistance training significantly improved outcomes, most likely due to the increased intensity of exercises. Although further research is required into the intensity of exercise, the meta-analysis suggests that moderate intensity exercise is recommended for cancer survivors. It is currently not standard practice for cancer survivors to be prescribed exercises post treatment, despite evidence by Fong et al that exercise improves physical function and quality of life. Exercise for cancer survivors should be the norm, rather than the exception. Further research on type and intensity of exercise across a variety of tumour streams will assist

clinicians in appropriate exercise prescription. “
“Summary of: Langer D, et al (2012) Exercise training after lung transplantation improves participation in daily activity: a randomized controlled trial. Am J Transplant 12: 1584–1592. [Synopsis prepared by Kylie Hill, CAP editor.] Question: In patients immediately following lung transplant, does three months of supervised exercise training confer changes in physical activity during daily life, functional exercise capacity, muscle force, health-related quality of life mafosfamide (HRQL), or forced expiratory volume in one second (FEV1)? Design: Randomised, controlled trial with concealed allocation in which investigators responsible for collecting the outcome measures were blinded to group allocation. Setting: Out-patient department of a hospital in Leuven, Belgium. Participants: Patients aged between 40 and 65 years who had an uncomplicated single or double lung transplant. Randomisation of 40 participants allocated 21 to the intervention group and 19 to the control group. Interventions: Participants in both groups received six individual counselling sessions of 15–30 minutes in duration, during which they were instructed to increase participation in daily physical activity.

Thus, Protein S does indeed function as a ligand for the Mer receptor expressed by RPE cells, and a fraction of this Protein S is produced by the RPE and CB. These effects notwithstanding, the PR loss seen in the Pros1fl/-/Trp1-Cre/Gas6−/− and Pros1fl/fl/Trp1-Cre/Gas6−/− mice is still less severe than that of the Mertk−/− mice ( Figure 2B). We therefore used a second, nervous-system-restricted Cre driver, Nestin-Cre ( Tronche et al., 1999), which should recombine

floxed Pros1 alleles in all cells check details of the retina, including the RPE and CB. We again crossed this driver with both Pros1fl/fl and Pros1fl/- mice, which were simultaneously either Gas6+/+, Gas6+/−, or Gas6−/−. Most dramatically, retinae from Pros1fl/-/Nes-Cre/Gas6−/−

mice, in which retinal expression of both ligands is eliminated, display a severe loss of ONL nuclei that is statistically identical to the PR death seen in the Mertk−/− selleck screening library mutants ( Figure 2C, solid dark green curve). Adding a single wild-type Gas6 allele back to this genotype—to generate Pros1fl/-/Nes-Cre/Gas6+/− mice—completely restores the ONL to a wild-type thickness ( Figure 2C, solid light green curve, outlined data points). Thus, a retina with no neural Protein S and no Gas6 displays the same severe PR loss and retinal degeneration seen in a retina with no Mer; but a retina with no neural

all Protein S and only half the normal level of Gas6 has a normal number of PRs ( Figure 2C). This is also the case for a retina of the reciprocal genotype, Pros1fl/-/Gas6−/−, which has no Gas6 and only half the normal level of Protein S; this retina also has an ONL of normal thickness that extends all the way to its ends ( Figures S1G and S1H). In summary, only half the normal retinal level of either ligand—in the complete absence of the other—is sufficient to maintain a normal number of PRs in the 12-week mouse retina. There is no difference in PR number across the retina between Pros1fl/-/Nes-Cre/Gas6+/− mice and Pros1fl/-/Nes-Cre/Gas6+/+ mice, both of which display a wild-type profile ( Figure 2C, light green curves). In contrast, Pros1fl/fl/Nes-Cre/Gas6−/− mice display PR degeneration that is comparable to the Mertk−/− and Pros1fl/-/Nes-Cre/Gas6−/− mice, but only in the center of the retina—from ∼35%–65% of the retinal DV axis ( Figure 2C, dark green dashed curve). At more peripheral positions—both ventral and dorsal from the center—PR degeneration becomes progressively less pronounced in these Pros1fl/fl/Nes-Cre/Gas6−/− mice. This effect is due to incomplete recombination of the floxed Pros1 allele under the influence of the Nestin-Cre driver at peripheral retinal locations.

One measure of trial-to-trial covariation between neuronal signals and choice behavior is choice probability (Britten et al., 1996), which quantifies the probability that an ideal observer of the neuron’s firing rate would correctly predict the

choice of the subject. We computed the choice probability for firing rates of delay period cells. For each cell, we focused on the last 400 ms of the delay period, using only memory trials in which the instruction was to orient to the cell’s preferred side. Consistent Luminespib datasheet with the SSI delay period analysis, we found that an ideal observer would, on average, correctly predict the rat’s side port choice 64% of the time. The cell population is strongly skewed above the chance prediction value of 0.5, with 75% of cells having a choice probability value above 0.5 (Figure 4F). Twenty-seven percent of cells had choice probability values that were,

individually, significantly Quisinostat above chance (permutation text, p < 0.05). We used red and blue LEDs, placed on the tetrode recording drive headstages of the electrode-implanted rats, to perform video tracking of the rats' head location and orientation (Neuralynx; MT). Two thirds of the delay period neurons (53/89) were recorded in sessions in which head tracking data was also obtained. Figure 5A shows an example of head angular velocity data for left memory trials in one of the sessions, aligned to the time of the Go signal. There is significant

trial-to-trial variability in the latency of the peak angular velocity as the animal responds to the Go signal and turns toward a side port to report below its choice. As shown in data from the example cells of Figure 3, and an example cell in Figure 5B, many neurons with delay period responses also fire strongly during the movement period, and the latency of each neuron’s movement period firing rate profile can vary significantly from trial to trial. To quantitatively estimate latencies on each trial, we used an iterative algorithm that finds, for each trial, the latency offset that would best align that trial with the average over all the other trials (Figures 5A and 5B; see Experimental Procedures for details). Firing rate latencies and head velocity latencies were estimated independently of each other using this algorithm. We then computed, for each neuron, the correlation between the two latency estimates (e.g., Figure 5C). We focused this analysis on correct contralateral memory trials of delay period neurons (as in Riehle and Requin, 1993). Of 53 delay period cells analyzed, 23 of them (43%) showed significant trial-by-trial correlations between neural and behavioral latency (Figure 5D). Furthermore, as a population, the 53 cells were significantly shifted toward positive correlations (mean ± SE, 0.36 ± 0.05, t test p < 10−8).

This study was supported by NIH grants R01MH085828 (C.E.L.S., W.A.S.) and R01MH058847 (W.A.S.). “
“Two complementary principles, segregation of function and dynamic integration, coexist within the brain (Friston, 2002). Segregation of function has been recognized for well over 100 years. Thus, there exist different neural

systems specialized for sensory processing (in multiple modalities), motor control, and various aspects of cognition (e.g., attention, episodic memory, affective evaluation). Neuroimaging, first with positron emission tomography (PET), and later with functional magnetic resonance imaging (fMRI), has greatly advanced our understanding of functional segregation within the human brain. Remarkably, the topography of segregated functional systems can be discerned by analysis of spontaneous covariation of the blood oxygenation level (BOLD) signal acquired in the “resting state,” that is, in the absence Target Selective Inhibitor Library solubility dmso of imposed task structure (Biswal et al., 1997, Deco and Corbetta, 2011, Fox et al., 2005 and Smith et al., 2009). These topographies now are widely referred to as resting state networks (Beckmann et al., 2005). However, effective behavior depends on the dynamic integration of sensory, motor, and cognitive functions at multiple spatial and temporal scales (Tononi, 2004). The low find protocol temporal resolution of fMRI precludes studying integration

on a timescale well matched to behavior. Hence, our understanding of principles governing dynamic integration across anatomically segregated functional domains remains limited. Invasive electrophysiology (extracellular spike or local field

potential recording) offers a means of studying network interactions at high those temporal resolution (Engel et al., 2001) but is restricted in spatial coverage, which prevents simultaneous monitoring of multiple, distributed brain networks. Noninvasive electrophysiology (electroencephalography [EEG] and magneto-encephalography [MEG]) offers high temporal resolution and wide coverage, thereby enabling the study of network interactions on a behaviorally relevant timescale (Varela et al., 2001). Recent studies using high temporal resolution methods suggest that the apparent temporal stationarity of resting state networks (RSNs), as observed through the slow temporal filter of the BOLD signal, obscures a much richer structure both in the time- and frequency-domain. (Brookes et al., 2011a, Brookes et al., 2011b, de Pasquale et al., 2010, He et al., 2008, Liu et al., 2010, Mantini et al., 2007 and Nir et al., 2008). These complex spatio-temporal patterns theoretically provide the substrate for the integration of information within and across networks during active behavior. However, little information currently exists regarding how this communication manifests in the resting state. The present study builds on the observation that RSNs, when studied at high temporal resolution with MEG (de Pasquale et al.

As in covert attention, overt attention also involves the visual selection of a target, and all of its component visual features, to the exclusion of other stimuli, as in our opening example. To achieve ZD1839 accurate visual guidance of saccades, saccades that incorporate the target’s component visual features, this must be true (e.g., Schafer and Moore, 2007). Correspondingly, as in covert attention, overt attention is accompanied by a selective enhancement of visual cortical signals (e.g., Moore and Chang, 2009), an effect that is consistent with the perceptual

enhancement known to occur at the target of gaze shifts (Deubel and Schneider, 1996). In other words, there are perceptual effects that accompany both types of attention, as well as neural correlates of those effects, in spite of the clear differences in motor outcome. Therefore, future studies might include a comparison of FEF activity, including its synchrony with other brain structures, between tasks in which attention is directed to (identical) visual stimuli with or without the execution of a gaze shift. “
“As a child growing up in New Haven, CT and Palo Alto, CA, Chi-Bin Chien was so academically gifted that he skipped straight Selleck Epacadostat from the third to the eighth grade and, at the unbelievable age

of 12, entered Johns Hopkins University as a Physics major. He was accepted to do graduate work in Physics at Caltech tuclazepam at the age of 15 but was considered too young to enter the program, so he took a fellowship at Cambridge University for a year. At 16, he began his PhD studies with the experimental physicist Jerry Pine, who had recently turned his attention to neurobiology and had pioneered the development of multielectrode arrays for studies of neuronal networks in vitro. Chi-Bin’s gift was not just his scintillating brilliance, because underneath he was a truly motivated scientist who was prepared to take practical and laborious steps to reach a distant goal. In the Pine laboratory, he designed

an elegant apparatus that was sensitive enough to measure single action and synaptic potentials in cultured neurons using voltage-sensitive dyes (Chien and Pine, 1991). Consideration of how the neural networks in his experimental dishes made connections with each other sparked Chi-Bin to choose the area of research in which he made most of his major contributions to knowledge: how the nervous system wires up in development. That he was interested in exploring this problem in vivo was the main reason we were lucky enough to attract Chi-Bin to work with us at UCSD. Chi-Bin made a number of remarkable innovations in our laboratory. For example, he developed a viewing chamber in which it was possible to observe single Xenopus retinal axons growing in the brain while washing various pharmacological reagents in and out as a way of probing the signaling systems that growth cones use to navigate correctly.

That is, not only must the control system determine what task is best to perform, but also the amount of control that must be allocated to that task so as to optimize EVC. This follows from the assumption that control is costly, as discussed earlier (see Figure 4). There is longstanding

evidence for adaptive adjustments in control in the behavioral literature, for example changes in the speed-accuracy tradeoff observed following errors in simple decision tasks (see Danielmeier and Ullsperger, 2011). Gratton et al. (1992) suggested that such adaptive adjustments extend to the allocation of attention, showing check details that the response to an incongruent stimulus is faster when it follows another incongruent stimulus than when it follows a congruent one. This was interpreted as evidence of an enhancement of attention to the task-relevant dimension in response to the interference produced by a prior incongruent one. In computational work, Botvinick et al. (2001) demonstrated that the behavioral effects described above could be explained by a mechanism that monitors conflict elicited by lapses in performance and/or interference and uses this to adjust the intensity of the task-relevant control signals in order to maintain task performance. However, the EVC model makes a stronger claim: that such adjustments

serve to optimize the allocation of control. A modest, but growing corpus of work has begun to address this stronger claim and its Obeticholic Acid relation to dACC function. Optimization of Control Intensity. The most extensive analyses of control optimization have focused on simple two-alternative choice tasks, such as those used to demonstrate adaptive changes in the speed-accuracy tradeoff mentioned above. Such tasks have been modeled extensively using simple accumulator models, in which the intensity of the control signal influences two parameters of the decision process:

the decision threshold and initial bias. Together, these determine the speed-accuracy tradeoff. Botvinick et al. (2001) showed Adenosine that monitoring response conflict in such models and using this to adjust the intensity of the control signal accurately accounted for adaptive changes in the speed-accuracy tradeoff observed in behavior. In that model, the intensity of the control signal determined the decision threshold. More recently, formal analyses by Bogacz et al. (2006) have shown that there is an optimal threshold (i.e., speed-accuracy tradeoff) that maximizes reward rate for a given set of task conditions, and similarly for initial bias. Furthermore, behavioral studies show that participants adapt their behavior to changes in task conditions in ways that often approximate adoption of the optimal threshold and bias (reviewed in Cohen and Holmes, 2013).

In wild-type animals, ALM neurons have a single anteriorly directed process ( Figures 8B and 8C). In mutants with decreased Wnt signaling, ALM neurons exhibit either of two defects, with some neurons having both an anterior and a posterior process (bipolar ALMs) while others have a single posteriorly directed process (reversed ALMs) ( Figures 8B and 8C) ( Fleming et al., 2010 and Prasad and Clark, 2006). The prevalence of bipolar and reversed ALM neurons differs among Wnt mutants. These differences

in ALM defects likely result from the fact that C. elegans has five Wnt ligands, which have distinct effects on ALM polarity. For example, two prior studies showed that the effects of two Wnts (CWN-1 and EGL-20) on ALM polarity are antagonized by a third Wnt (LIN-44) ( Fleming et al., 2010 and Prasad and Clark, 2006). Thus, the precise ALM phenotype observed is determined by how Tanespimycin cell line each mutation alters signaling

by the different Wnt ligands. To further investigate PD-0332991 solubility dmso if RIG-3 plays a role in Wnt signaling, we analyzed the effect RIG-3 inactivation on ALM polarity in several genetic backgrounds. Although ALM polarity was unaltered in rig-3 single mutants, the rig-3 mutation significantly altered ALM polarity defects caused by other Wnt pathway mutations in double and triple mutants. Inactivating RIG-3 in cwn-1; egl-20 double mutants decreased the severity of ALM polarity defects: ALM reversals were significantly reduced in second cwn-1; egl-20; rig-3 triple mutants (p < 0.01, Fishers exact test), while the number of bipolar ALMs was unaffected (p = 0.21, Fishers exact test). Inactivating RIG-3 in mig-14 Wntless mutants decreased ALM reversals and increased bipolar ALMs ( Figures 8B and 8C). The different outcome in mig-14 mutants likely results from the fact that MIG-14 is required for secretion of all Wnt

ligands. By contrast, the rig-3 mutation had no effect on ALM polarity in two strains lacking CAM-1, i.e., cam-1; rig-3 double mutants and cam-1 mig-14; rig-3 triple mutants ( Figure 8C). These results lead to three conclusions. First, RIG-3 plays an important role in Wnt regulation of ALM polarity. Second, CAM-1 is absolutely required for the effects of RIG-3 on ALM polarity. Third, the effects of RIG-3 on ALM polarity and on ACR-16 levels at the NMJ can both be explained by changes in Wnt signaling. Our results lead to six primary conclusions. First, RIG-3 acts in motor neurons to prevent a form of postsynaptic plasticity that is induced by aldicarb treatment. Second, inactivating RIG-3 has no effect on baseline synaptic transmission, suggesting that the function of RIG-3 is required only during aldicarb-induced plasticity. Third, the synaptic potentiation observed in rig-3 mutants is mediated by aldicarb-induced accumulation of postsynaptic ACR-16 nAChR receptors. Fourth, RIG-3 decreases the number of mobile ACR-16 receptors available for recruitment into postsynaptic receptor fields.

, 2007) and neurosteroids (which are brain-synthesized metabolites of ovarian and adrenal cortical steroid hormones) act as anesthetics through an action on δ-GABAARs

(Stell et al., 2003). Indeed, the loss of δ-GABAARs is associated with an attenuated response to neurosteroid-induced anesthesia (Mihalek et al., 1999). Other important general anesthetics such as propofol and isoflurane enhance tonic BAY 73-4506 manufacturer inhibition in hippocampal neurons (Bai et al., 2001), thalamic relay neurons (Jia et al., 2008b), and neocortical neurons (Drasbek et al., 2007). However, the amnesia-inducing effect, but not the anesthetic potency of isoflurane, is altered in α4 knockout mice, which also lack δ-GABAARs on the cell surface (Rau et al., 2009), demonstrating that extrasynaptic GABAARs are not a primary site of action for all anesthetics. Neurosteroids are among the most powerful regulators of GABAAR function in the CNS (Belelli and Lambert, 2005, Chisari Small molecule library et al., 2010, Mitchell et al., 2008 and Reddy, 2010). The first example of this robust modulatory effect was discovered nearly 30 years ago (Harrison and Simmonds, 1984) for the synthetic steroid alphaxalone (5α-pregnan- 3α-ol-11,20 dione). Shortly after, it was demonstrated that a metabolite of the ovarian steroid hormone progesterone (allopregnanolone, also called 3α-hydroxy-5α-pregnan-20-one, or 3α,5α-tetrahydroprogesterone, or 5α-pregnan-3α-ol-20-one,

or 5α3α-THPROG) and a metabolite of the stress steroid deoxycorticosterone (aka 5α3α-THDOC) are potent barbiturate-like MTMR9 ligands of GABAARs (Majewska et al., 1986). Our first collaborative research (Stell et al., 2003) demonstrated that δ-GABAARs are a preferred site of action for neurosteroids at low (nanomolar) concentrations. This preferred action probably reflects a simple property of these receptors: GABA is not an efficacious agonist at δ-GABAARs (Chisari et al., 2010), which means that the coupling of GABA binding to channel opening is not efficient. Because neurosteroids increase the likelihood that GABA will open the channel

(Chisari et al., 2010), they can enhance the efficacy of GABA at δ-GABAARs and thus modulate receptor activity, while this is less likely at other GABAARs where GABA is already an efficacious agonist. Perhaps δ-GABAARs are the preferred site of action for paracrine neurosteroid signaling where the neurosteroids synthesized in another cell (e.g., astrocyte) must travel through the extracellular space to act on extrasynaptic δ-GABAARs. Neurosteroid synthesis in astrocytes is regulated by the mitochondrial 18 kD translocator protein TSPO (the peripheral benzodiazepine receptor by its former name) for which the drug XBD173 is an excellent nonsedative anxiolytic and antipanic agent (Rupprecht et al., 2009). The mitochondrial TSPO is also in CNS neurons where it may mediate autologous effects of neurosteroids on neuronal excitability in brain slices following benzodiazepine (Tokuda et al.