mtor floxed mice

on a C57BL/6 background (kindly provided by Dr. Sara C. Kozma, University of Cincinnati) were crossed to cytomegalovirus promoter (a ubiquitously expressed promoter)-Cre mice to generate mtor+/− mice ( Sauer and Henderson, 1988). Eif4ebp1 KO mice were crossed with mPER2::LUC transgenic reporter mice ( Yoo et al., 2004) to obtain Eif4ebp1−/−:mPER2::LUC mice. Animals were maintained in the animal facility at McGill University in accordance with institutional guidelines. All procedures were approved by the Institutional Animal Care and Use Committee. Mice were cannulated in the lateral ventricles using the techniques described by Cao et al. (2008). The coordinates (posterior, 0.34 mm from bregma; lateral, 0.90 mm from the midline; dorsoventral, −2.15 mm from bregma) were used to place the tip of a 24 gauge guide cannula into the lateral ventricle. To disrupt VIP signaling, PG99-465 selleckchem (100 μM, 4 μl; Bachem, Switzerland) was infused through

the cannula at ZT15. Control animals were infused with physiological saline (4 μl). Eight- to 10-week-old male mice were individually housed in cages equipped with running wheels. Wheel rotation was recorded using PD-1/PD-L1 inhibition the VitalView program (Mini Mitter, Bend, OR, USA) (Hood et al., 2010). For the “jet lag” experiments, mice were entrained to a 12 hr/12 hr LD cycle (12 lx) for 10 days. On the 11th day, the LD cycle was either advanced for 6 hr or delayed for 10 hr, and animal behavior was recorded for 10 days following the LD cycle shift. For the constant light (LL) experiments, mice were first kept in common cages under LL (200 lx) for 14 days and then transferred during to running-wheel cages in LL (55 lx) to record their intrinsic rhythms for 14 days. The actograms of wheel-running activities were analyzed using the ActiView software (Mini Mitter) and

the ClockLab software (Actimetrics, Wilmette, OR, USA). Under indicated conditions, mice were sacrificed and brain tissue was harvested. SCN sections were processed and immunostained for 4E-BP1, p-4E-BP1, PER1, PER2, AVP, and VIP as previously reported (Cao et al., 2008, Cao et al., 2010 and Cao et al., 2011). Bright-field microscopy images were captured using a digital camera mounted on an inverted Zeiss microscope (Oberkochen, Germany). Confocal microscopy images were captured using a Zeiss 510 Meta confocal microscope. See Supplemental Information for antibody information and image quantitation methods. The SCN tissue was excised using a 700 μm tissue punch and frozen on dry ice. SCN tissue was pooled from five animals per condition. Brain tissue was homogenized with a pestal grinder (Fisher Scientific Limited, Nepean, Canada) and lysed using a lysis buffer previously reported (Lee, 2007). Western blotting analysis was performed as described (Dowling et al., 2010). Brain polysome profiling was performed as described (Gkogkas et al., 2013).

scapularis within 48 h of infestation for at least one month. It is important that products used to control tick infestations be effective at a level greater than 90%, in order to provide relief from blood loss and irritation associated with tick bites (Marchiondo et al., 2013 and Dryden and Payne, 2004). The oral route of administration may be preferred by some owners over topical parasiticide products. For instance, the efficacy of some topical products may be affected by bathing or swimming, or there may be a period of time in which the application site DNA Damage inhibitor should be avoided by pet owners or other household animals (Dryden and Payne, 2004). Also, the density and length of

the dog’s hair coat does not affect the application of an oral product as it can with a topical product. The chewable formulation of Nexgard® is also advantageous in that it is palatable and voluntarily consumed by dogs, making it easy and Androgen Receptor Antagonist convenient for owners to administer. This study demonstrated the efficacy of

a single oral dose of afoxolaner against I. scapularis. Existing tick infestations were rapidly cleared and there was a residual protection against ticks for at least a month. The work reported herein was funded by Merial Limited, GA, USA. All authors are current employees or contractors of Merial. All studies were funded by Merial Limited. The authors gratefully acknowledge the staff at TRS Labs, Inc. (Athens, GA, USA) and at Merial Limited for their help in conducting the studies to a high professional standard; and also acknowledge Mike Murray, Lenaig Halos and Frederic Beugnet, Veterinary Parasitologists, for the scientific editing of the manuscript. “
“Ripicephalus Adenosine sanguineus sensu lato, the brown dog tick, most probably originated in Africa, but currently has a world-wide distribution and is an important

parasite of dogs and other domestic animals ( Dantas-Torres, 2010). This tick species is an important vector of a diverse range of pathogens, such as Babesia, Cercopithifilaria, Hepatozon, Ehrlichia, and Rickettsia ( Dantas-Torres, 2010 and Gray et al., 2013). Control of tick infestations can be a primary means of preventing these infections ( Beugnet and Franc, 2012, Otranto et al., 2009a and Otranto et al., 2009b) and limiting other adverse consequences of tick infestations, such as flaccid paralysis ( Blagburn and Dryden, 2009 and Otranto et al., 2012). This article describes a series of 2 studies that were performed to demonstrate the efficacy of afoxolaner, a novel insecticide–acaricide, in an oral chewable formulation (Nexgard®, Merial) against R. sanguineus. Two studies were conducted to assess the efficacy of afoxolaner against R. sanguineus sensu lato using two tick strains from different parts of the world. Study A was performed in South Africa, and Study B in Australia.

We then computed the Spearman’s correlation between linear distance and either relative spike timing or gamma phase to determine how strongly these measures covaried. To determine the relationship between place field distance and correlation with gamma phase and spike timing, we divided the data into roughly four equally sized groups based on the distance

between place field peaks. We then computed the Spearman’s correlation between linear distance and either relative spike timing or gamma phase for each group. For quiescent SWRs, we used place fields recorded during the preceding behavioral session for pairwise decoding. To measure place field locations, we calculated an occupancy-normalized linearized place field for each cell

using 2-cm bins and smoothed IOX1 price with a 4 cm SD Gaussian curve. SWRs were excluded. A peak rate of 3 Hz or greater was required for a cell to be considered a place cell. Candidate replay events were defined as SWRs during which at least five place cells fired at least one spike each. We determined the sequential representation of position during a candidate replay event using a simple Bayesian decoder that has been described in detail before (Karlsson and Frank, 2009). Briefly, each event was divided into 15 ms bins and for each bin with at least one spike we calculated the spatial probability distribution using an uninformative prior. To determine whether the temporal sequence of decoded spatial probability distributions was a significant memory replay many we compared the regression BMS-354825 nmr of spatial locations with temporal bin to 10,000 regressions

in which the order of the bins was shuffled. The p value for each candidate event was defined as the proportion of the shuffled R2 values that was greater than the R2 value of the actual event, and an event with p < 0.05 was considered to be significant. Decoding was done with templates for both the animal’s current W-track and where applicable, the previously experienced W-track environment, in order to minimize false negatives. The R2 and the p value are correlated measures (Spearman ρ = −0.78). We focused on the p value measurement to quantify the improvement in coherence associated with significant replay events, although our results were similar when examined as a function of R2 values. To ask how gamma phase locking and coherence varied as a function of replay significance, we computed the phase locking and average coherence across significant and nonsignificant events. We used a permutation test to determine when the difference between significant and nonsignificant candidate events was significant. We compared the measured difference to the difference computed on 1,000 permutations of the p value associated with each candidate event. We thank members of the Frank laboratory, V. Sohal, S. Leutgeb, P. Janak, M. Brainard, and P. Sabes for comments on the manuscript. This work was supported by an NSF graduate research fellowship to M.F.C.

To assess whether the delayed bending of the posterior region represented mechanical damping by the external viscous fluid or internal delays within the neuromuscular network, we studied worms in fluids of different viscosity (Figures 5D–5F). We found that the bending delay was roughly constant, GSK2656157 mw ∼300 ms, in fluids ranging from 1 mPa·s (the viscosity of water) to ∼100 mPa·s. In more viscous fluids, the bending delay began to increase,

becoming ∼1 s at 300 mPa·s. These results suggest that ∼300 ms represents an upper bound for delays within the neuromuscular network, which are rate-limiting at low viscosities. These neuromuscular delays might reflect delays in synaptic transmission and/or the limiting speed of muscle contraction. The C. elegans wiring selleck diagram offers a small number of candidate cell types within the motor circuit that might play roles in generating or propagating a local proprioceptive signal: the A-type cholinergic motor

neurons, B-type cholinergic motor neurons, the D-type GABAergic motor neurons, and muscle cells. One neuron outside the core motor circuit, the DVA interneuron, has also been shown to exhibit proprioceptive properties ( Li et al., 2006). We sought to determine which cell type was responsible for coupling the bending activities of adjacent body regions through proprioception. First, we trapped transgenic worms that expressed halorhodopsin in all cholinergic motor neurons (Punc-17::NpHR) in the pneumatic devices and illuminated them with green light. We found that light-induced hyperpolarization of the cholinergic neurons prevented the posterior body regions from following induced changes in the curvature of the anterior region ( Figures 6A–6C and Movie S8). Instead, optogenetic inactivation of the cholinergic neurons locked the posterior region in the posture as it was immediately preceding illumination. Second, we studied vab-7 mutants, which have specific defects PDK4 in the morphology of the dorsal B-type

cholinergic motor neurons. In these mutants, the DB neurons reverse the orientation of their axons so that they project anteriorly instead of posteriorly ( Esmaeili et al., 2002) ( Figure S3A) The vab-7 mutation does not affect the ventral B-type motor neurons. During unrestrained forward movement, the bending wave near the head of vab-7 mutants was normal. However, the bending wave that propagates to posterior regions was biased toward the ventral side ( Figures S3B and S3D). When we trapped vab-7 mutants in the pneumatic channels, the posterior region was only able to follow channel bending to the ventral side, not to the dorsal side ( Figures S3C, S3F, and S3G). These results suggest that the dorsal and ventral B-type cholinergic motor neurons are each responsible for propagating dorsal and ventral curvatures to posterior body regions.

For each cell, data were filtered at 1 kHz and analyzed by using template-based mEPSC detection algorithms implemented in AxoGraph X 1.0 (AxoGraph Scientific). The threshold for detection was set at three times the baseline SD from a template of 0.5 ms rise time and 3 ms decay. The preparation of lentiviral particles expressing different VGLUTs

was done as described CH5424802 concentration (Lois et al., 2002). Briefly, HEK293T cells were cotransfected with 8 μg shuttle vector F(SYN)UGW-RBN bearing cDNAs for the different VGLUTs and the mixed helper plasmids pCMVdR8.9 and pVSV-G (5 μg each) with Fugene 6 transfection reagent (Roche Diagnostics, Indianapolis, IN). After 48 hr the cell culture supernatant was collected and cell debris was removed by filtration. Aliquots of the filtrate check details were flash-frozen in liquid nitrogen and stored at −80°C. Estimation of the titer was done on mass cultures of wild-type hippocampal neurons. For infection of the neurons for experiments 300–500 μl of the viral solution (0.9–1.8 × 106 IU/ml) was used 18–24 hr after plating. Five different shRNAs from the TRC-Mm1.0 library targeted against endophilin A1 in the pLKO.1 vector were obtained from Open Biosystems (Huntsville, AL), as well as a control sequence against eGFP. Lentiviral particles were prepared as described above.

Estimation of the titer was done on mass cultures of wild-type hippocampal neurons by applying puromycin (2 μg/ml) and counting the numbers of surviving cells after 48 hr. Equal amounts of control and shRNA viral particles (∼2 × 106 IU) were then applied to mass cultures of hippocampal neurons. After 14 days in vitro cells were harvested and western blot analysis was used to assess the amount of reduction in endophilin A1 protein. We thank Hongmei Chen for help with mouse care and genotyping, Hui Deng and Marife Arancillo for help with cell culture and virus production, Dieter Moechars for supplying the

VGLUT2 knockout mice, Etienne Herzog for supplying endophilin antibodies and cDNA, and Amy Shore L-NAME HCl for help with molecular cloning and design of Figure 8. This work was supported by a Helen and Rush Record fellowship (M.C.W.), by a Human Frontier Science Program Research Grant, by the European Research Council grant SYNVGLUT, and by the German Research Council Excellence Cluster Neurocure (C.R). “
“Animals actively gather sensory information through self-generated movements. For example, eye movements are used to foveate interesting regions of visual space. Self-generated eye movements, therefore, in part determine the visual sensory input that falls upon the retina. Active sensing is also obvious for somatosensation, where finger movements are used to explore object shape and texture. Through internally generated movements, animals thus determine a large part of the sensory information that they receive.

This hypothesis could be tested by simultaneous measurement of the vertical distribution of larvae ( Blackwell and King, 1997 and Mullens and Rodriguez, 1992) and thermal regimes in muck heaps versus other available larval

habitats. Additional studies have also demonstrated that exposure of Culicoides larvae to high ambient temperatures can alter vector competence parameters in resulting adults ( Mellor et al., 1998 and Wittmann et al., 2002). Together with an increased interest in the potential role of environmental acquired microbiota in competence and/or survivorship of vector species of Culicoides ( Campbell et al., 2004, Morag et al., 2012 and Nakamura et al., 2009), microhabitat investigations of larvae are clearly Selleckchem HKI-272 of significant interest in the Palearctic region. Although a higher average temperature in the muck heap as HSP assay a result of covering may increase vector competence if Culicoides were able to escape following emergence under the tarpaulin, it may also lead to a higher mortality rate in larval Culicoides. Todd (1964) hypothesised that the observed reduction in S. calcitrans larval numbers was as a result of the high temperatures observed and a lack of oxygen available under the plastic coverings used. The effect of covering

muckheaps on the chemical composition of a muck heap, which has previously been shown to have a significant effect of the productivity of larval development habitats ( Zimmer et al., 2012), and other factors such as the impact on dissolved oxygen content may also influence Culicoides larval development Farnesyltransferase success and recruitment to the local adult population. While the larval habitats of subgenus Avaritia Culicoides have been characterised in the UK, they are difficult to delineate precisely at the farm level. Our understanding of the relationship between available developmental habitat and the absolute adult abundance of these species within farms therefore remains extremely poor. In the case of C. obsoletus and C. scoticus,

which are patchily distributed across a wide-variety of breeding habitats and across a wide geographic area, these studies would be challenging to perform. The localised larval development sites of C. dewulfi and C. chiopterus, however, represent a habitat the extent of which can be quantified accurately and may provide a highly malleable experimental system as has already been implemented with the Australian BTV vector C. brevitarsis ( Bishop et al., 2005 and Campbell and Kettle, 1976). The practical utility of such a system would in part be dependent upon future studies assessing the role of each of these species in the transmission of arboviruses, since these roles remain poorly defined at present ( Carpenter et al., 2008b).

Many inhibitory interneurons display tonic activation over the entire duration of odor stimulation in contrast to others that Onalespib remain hyperpolarized (Figure 7A, bottom). Such patterns of activity are well described by our model (Figure 7A, top). In this example, for the network with nonunique coloring, one group of LN neurons remained active

during the entire duration of stimulation while the two other groups of neurons switched between active and silent states. Why do LNs in the AL exhibit only a subset of the broad repertoire of patterns that the networks simulated here are capable of generating? The formalism we developed in our manuscript points us toward several possibilities. These dynamical patterns are likely to result from an intrinsic asymmetry within the AL subnetwork that gets activated in response to a specific odor. If only a subset of neurons receives strong activation during a particular odor stimulation, these neurons will dominate the response. Asymmetries in coupling strength can also result in the predominance of one group that would prevent switching between groups to occur. In addition, if the number of colors is large, a trajectory may never recur during odor stimulation. Hence the same

LN may not generate multiple bursts of spikes. We have shown that fast GABAergic inhibition mediated by GABAA receptors transiently synchronizes PN activity over a few cycles of the ensemble oscillatory response. A second important GS-7340 in vivo form of inhibition found in the AL mediated by slow GABAB receptors acts over a timescale in the range of hundreds of milliseconds (Wilson and Laurent, 2005). Experiments (MacLeod and Laurent, 1996) and models (Bazhenov et al., 2001a) have demonstrated that this type of interaction leads to lengthy epochs of time wherein individual

PNs are hyperpolarized and do not spike at all. Picrotoxin applied to the AL spares patterning caused by slow inhibition while abolishing oscillatory synchronization on a fast timescale. The timescales Resminostat separating the two forms of inhibition differ by approximately an order of magnitude. To explore how network structure leads to transient synchrony, a key dynamical variable involved in fine discrimination in the olfactory system (Stopfer et al., 1997), we focus here on fast inhibition while minimizing the effects of slow inhibition in the model. The repertoire of patterns generated by the inhibitory subnetwork in the locust AL forms a subset of the full range of patterns that can be generated by the networks simulated here. Feedforward architecture and coincidence detection mechanisms like those illustrated here are not unique to the insect olfactory system.

Besides the classical cannabinoid

check details receptors (CB1R/CB2R), there is growing evidence that TRPV1 channels also participate in eCB signaling (De Petrocellis and Di Marzo, 2010; Pertwee et al., 2010). TRPV1, originally VR1 for vanilloid receptor type 1 (Caterina et al., 1997), is a polymodal transient receptor potential (TRP) ion channel largely expressed in afferent peripheral sensory neurons, where its activation regulates synaptic transmission associated with pain sensation (Caterina and Julius, 2001). Interestingly, TRPV1 can bind lipophilic substances, such as AEA (Di Marzo et al., 2002). Of note, AEA is a partial agonist at the CB1R but a full agonist at TRPV1 channels (Smart et al., 2000; Zygmunt et al., 1999). In addition to their expression in the periphery, TRPV1 channels have been found in the CNS (Cristino et al., 2006, 2008; Mezey et al., 2000; Puente et al., 2011; Roberts et al., 2004; Tóth et al., 2005) (but see Cavanaugh et al., 2011), where they

appear to regulate synaptic function. Recent studies revealed that AEA acting on TRPV1 mediates a postsynaptic form of LTD (Figure 3A). This TRPV1-LTD has been observed in dopamine receptor-2 (D2)-positive medium spiny neurons of the nucleus accumbens (Grueter et al., 2010), in dentate granule cells (Chávez et al., 2010), and in the bed nucleus of the stria terminalis (Puente et al., 2011). In each case, activation of mGluR5, presumably via PLC (Liu et al., 2008) VX-770 and Ca2+ release from intracellular stores, promotes the synthesis of AEA that activates TRPV1 channels. In addition, TRPV1-LTD relies on AMPA receptor (AMPAR) endocytosis. These findings are consistent with the notion that

AEA can act as an intracellular messenger (van der Stelt and Di Marzo, 2005) but differs from a presynaptic, TRPV1-dependent LTD at glutamatergic synapses onto CA1 hippocampal interneurons (Gibson et al., 2008). While CB1Rs mediate excitatory and inhibitory synaptic plasticity, whether brain TRPV1 channels mediate inhibitory synaptic plasticity is unknown. There is also evidence that TRPV1 localizes to neuronal intracellular compartments like the Dipeptidyl peptidase endoplasmic reticulum, trans-Golgi network, and perhaps even vesicles ( Dong et al., 2010). The functional significance of such receptors warrants further investigation. Nonretrograde eCB signaling has been observed in other contexts. Repetitive activation of a subtype of neocortical GABAergic interneuron triggers a CB1R-dependent postsynaptic hyperpolarization, which reduced its excitability (Figure 3B) (Bacci et al., 2004). This slow self-inhibition resulted from activity-dependent rises in intracellular Ca2+, mobilization of 2-AG, and activation of CB1Rs that couple to a G protein-coupled inwardly rectifying K+ channel (Bacci et al., 2004; Marinelli et al., 2008).

A 3 min Vm trace during 3 successive CCW laps (Figure 2E) shows that each pass through the place field was accompanied by high AP firing rates as well as a clear subthreshold depolarization under that spiking (A.K. Lee et al., 2008, Soc. Neurosci., abstract [690.22]; Harvey et al., 2009). The sustained nature of these depolarizations suggests that spatially tuned spiking is not simply due to a short timescale coincidence detection mechanism. Some (Figure 2E, trace 1), but not all (trace 2), passes revealed spiking associated

with a series of large (to ∼−25 mV), long-lasting (∼100 ms) depolarizations (Kandel and Spencer, 1961, Wong and Prince, 1978, Traub and Llinás, 1979 and Takahashi and Magee, 2009) occurring rhythmically at ∼4–5 Hz (theta frequency). Figure 3 shows an intracellularly selleck chemical recorded silent cell that fired very few spikes in the maze and did not have a place field in either direction (Figures 3A–3D). CHIR-99021 mw CCW direction spiking occurred mostly during 1 lap (Figure 3C) and thus did not satisfy the consistency criterion for place fields (Experimental Procedures). An ∼3 min trace shows that the Vm was very flat as the animal moved around the maze (here ∼1.5 CW laps) (Figure 3E). An expanded trace (Figure 3E, above right) reveals ∼5 Hz, ∼5–10 mV subthreshold fluctuations. We estimated the net input into the

cell as seen at the soma as a function of the animal’s location. This was done for each direction of each cell as follows. We first removed all APs and any parts of the Vm trace isothipendyl directly attributable to the spikes themselves, i.e., parts representing spike-associated regenerative and/or other intrinsic processes at the soma as distinct from the inputs that triggered the spikes (see Figures S1A–S1C available online; Experimental

Procedures). This included removing (1) spike after-depolarizations (ADPs), which can be >5 mV and last for >20 ms for single APs and can accumulate for successive APs (Figures S1A and S1B; Kandel and Spencer, 1961, Wong and Prince, 1978, Traub and Llinás, 1979 and Jensen et al., 1996), and (2) the entirety of the slow, large, putatively calcium-based depolarizations that often follow a burst of APs, which can be >25 mV and last for >50 ms (Figure S1C; Kandel and Spencer, 1961, Wong and Prince, 1978 and Traub and Llinás, 1979). Then the remaining Vm trace was linearly interpolated across the gaps (Figures S1A–S1C) and the mean of the resulting trace as a function of location computed (Figure 4A, black). While the classical, i.e., mean spiking rate, place field (Figure 4A, red) represents the output of the cell, this mean “subthreshold field” reflects the spatially-modulated, net input into the cell’s soma. We determined the AP threshold of each cell as follows. The threshold for individual APs varies, especially (1) within a burst, rising with successive APs (Figure S1B; Kandel and Spencer, 1961), (2) during longer periods of depolarized Vm (e.g.

We evaluated the effects of input inactivation on the magnitude of tone responses as indicated by responses in the first 3 s bin after tone onset. We limited our

analysis to cells showing significant tone responses (Z > 2.58; p < 0.01) either before or after input inactivation. We found that 20% of PL cells (n = 34/172) were tone responsive prior to input inactivation, similar to our previous report ( Burgos-Robles et al., 2009). Inactivation of BLA and vHPC produced opposite effects. Averaging over all tone responsive neurons (n = 26/78, 33%), BLA inactivation significantly decreased tone responsiveness (t25 = 3.52 [paired]; p = 0.002; see Figure 2A, top, bottom). This effect was due to decreased tone responses of pyramidal neurons (t21 =

2.81 [paired]; p = 0.011; Figure 2A, bottom inset) and interneurons (t3 = 4.11 [paired]; p = 0.03; Figure S2). In contrast to Dinaciclib manufacturer BLA, vHPC inactivation increased tone responses (for example, see Figure 2B, top). Averaging over all tone responsive PL neurons (n = Y-27632 supplier 25/95, 26%), vHPC inactivation significantly increased tone responsiveness (t24 = −2.26 [paired] p = 0.03; Figure 2B, bottom). This effect was due to increased tone responses of pyramidal neurons (t18 = 2.12 [paired]; p = 0.048; Figure 2B, bottom inset) and not to interneurons (t5 = 0.75 [paired]; p = 0.48; Figure S2). These opposing effects of BLA and vHPC inactivation could be detected as early as 300 ms after tone onset. To evaluate within-cell changes, we tracked the tone responses Bay 11-7085 (TRs) of each cell before and after

inactivation in conditioned rats. Cells were classified as significantly tone responsive if they fired >2.58 SD, (p < 0.01) above baseline rate within the first 3 s bin. Inactivation of BLA caused the majority of the 26 PL cells to lose their TRs, a small proportion to become TR, and some to remain TR (Figure 2C). This suggests that BLA is the major route by which conditioned tones can influence PL. In contrast to BLA, inactivation of vHPC resulted in most of the 25 PL neurons either becoming TR or remaining TR, with a smaller number losing their TR (Figure 2D). Thus, despite the typical heterogeneity of single-cell responses, the pattern of responses we observed supports the idea that BLA communicates conditioned responses to PL, whereas vHPC gates those responses. To test whether these effects of BLA and vHPC converge onto single PL cells, we implanted a subset of rats with cannulas in both structures. Out of 10 PL neurons tested, we found 3 that were TR and 7 that were not TR. Notably, 2 of these 7 non-TR cells (from different rats) revealed evidence of BLA and vHPC convergence. Figure 3 shows the tone responses of these neurons, which were not initially TR (top panel), but became significantly TR after vHPC inactivation (middle panel).