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Utilizing the N-heterocyclic chalcogenones hexahydro-1,3-bis(2,4,6-trimethylphenyl)-2H-1,3-diazepine-2-thione (SDiazMesS) and hexahydro-1,3-bis(2,4,6-trimethylphenyl)-2H-1,3-diazepine-2-selone (SDiazMesSe) as halogen-bond acceptors, a total of 24 new cocrystals were prepared. The solid-state structures of the parent molecules were also determined, along with those of their acetonitrile solvates. Through the reaction of the chalcogen atom with molecular diiodine, a variety of S—I—I and Se—I—I fragments were formed, spanning a wide range of I—I bond orders. With acetone as a reaction solvent, molecular diiodine causes the oxidative addition of acetone to the chalcogen atom, resulting in new C—S, C—Se and C—C covalent bonds under mild conditions. The common halogen-bond donors, iodopentafluorobenzene, 1,2-, 1,3- and 1,4-diiodotetrafluorobenzene, 1,3,5-trifluorotriiodobenzene and tetraiodoethylene resulted in halogen-bond-driven cocrystal formation. In most cases, the analogous SDiazMesS and SDiazMesSe cocrystals are isomorphic.

Memories are encoded in neural ensembles during learning and stabilized by post-learning reactivation. Integrating recent experiences into existing memories ensures that memories contain the most recently available information, but how neural ensembles accomplish this critical process remains unknown. Here we show that in mice, a strong aversive experience drives the offline ensemble reactivation of not only the recent aversive memory but also a neutral memory formed two days prior, spreading the fear from the recent aversive memory to the previous neutral memory. We find that fear specifically spreads retrospectively, but not prospectively, to neutral memories across days. Consistent with prior studies, we find reactivation of the recent aversive memory ensemble during the offline period following learning. However, a strong aversive experience also increases co-reactivation of the aversive and neutral memory ensembles during the offline period. Finally, inhibiting hippocampal reactivation during this offline period abolishes the spread of fear from the aversive experience to the neutral memory. Taken together, these results demonstrate that strong aversive experience can drive retrospective memory integration through the offline co-reactivation of recent memory ensembles with memory ensembles formed days prior, providing a neural mechanism by which memories can be integrated across days.

The reaction of pyridine-thiocarboxamides with I2 provided a variety of novel heterocyclic products as iodide, triiodide, and/or pentaiodide salts. Bismuth triiodide was incorporated as a crystallization aid to access other structural types.

Severe stress can produce multiple persistent changes in defensive behavior. While much is known about the circuits supporting stress-induced associative fear responses, how circuit plasticity supports the broader changes in defensive behavior observed after severe stress remains unclear. Here, we find that stress-induced plasticity in the ventral hippocampus (vHC) and basolateral amygdala (BLA) support doubly dissociable defensive behavioral changes. Stress-induced protein synthesis in the BLA was found to support lasting enhancements in stress sensitivity but not enhancements in exploratory anxiety-related behaviors, whereas protein synthesis in the vHC was found to support enhancements in anxiety-related behavior but not enhancements in stress sensitivity. Like protein synthesis, neuronal activity of the BLA and vHC were found to differentially support the expression of these same defensive behaviors. Lastly, blockade of associative fear had no impact on stress-induced changes in anxiety-related behavior. These findings highlight that multiple memory-systems support stress-induced defensive behavior changes.

By varying the halogen-bond-donor molecule, 11 new halogen-bonding cocrystals involving thiourea or 1,3-dimethylthiourea were obtained, namely, 1,3-dimethylthiourea–1,2-diiodo-3,4,5,6-tetrafluorobenzene (1/1), C6F4I2·C3H8N2S, 1, thiourea–1,3-diiodo-2,4,5,6-tetrafluorobenzene (1/1), C6F4I2·CH4N2S, 2, 1,3-dimethylthiourea–1,3-diiodo-2,4,5,6-tetrafluorobenzene (1/1), C6F4I2·C3H8N2S, 3, 1,3-dimethylthiourea–1,3-diiodo-2,4,5,6-tetrafluorobenzene–methanol (1/1/1), C6F4I2·C3H8N2S·CH4O, 4, 1,3-dimethylthiourea–1,3-diiodo-2,4,5,6-tetrafluorobenzene–ethanol (1/1/1), C6F4I2·C3H8N2S·C2H6O, 5, 1,3-dimethylthiourea–1,4-diiodo-2,3,5,6-tetrafluorobenzene (1/1), C6F4I2·C3H8N2S, 6, 1,3-dimethylthiourea–1,3,5-trifluoro-2,4,6-triiodobenzene (1/1), C6F3I3·C3H8N2S, 7, 1,3-dimethylthiourea–1,1,2,2-tetraiodoethene (1/1), C6H16N4S2·C2I4, 8, [(dimethylamino)methylidene](1,2,2-triiodoethenyl)sulfonium iodide–1,1,2,2-tetraiodoethene–acetone (1/1/1), C5H8I3N2S+·I−·C3H6O·C2I4, 9, 2-amino-4-methyl-1,3-thiazol-3-ium iodide–1,1,2,2-tetraiodoethene (2/3), 2C4H7N2S+·2I−·3C2I4, 10, and 4,4-dimethyl-4H-1,3,5-thiadiazine-3,5-diium diiodide–1,1,2,2-tetraiodoethene (2/3), 2C5H12N4S2+·4I−·3C2I4, 11. When utilizing the common halogen-bond-donor molecules 1,2-, 1,3-, and 1,4-diiodotetrafluorobenzene, as well as 1,3,5-trifluoro-2,4,6-triiodobenzene, bifurcated I...S...I interactions were observed, resulting in the formation of isolated rings, chains, and sheets. Tetraiodoethylene (TIE) provided I...S...I cocrystals as well, but further yielded a sulfonium-containing product through the reaction of the S atom with TIE. This particular sulfonium motif is the first of its kind to be structurally characterized, and is stabilized in the solid state through a three-dimensional I...I halogen-bonding network. Thiourea reacted with acetone in the presence of TIE to provide two novel heterocyclic products, again stabilized in the solid state through I...I halogen bonding.

Epitranscriptomic mechanisms linking tRNA function and the brain proteome to cognition and complex behaviors are not well described. Here, we report bi-directional changes in depression-related behaviors after genetic disruption of neuronal tRNA cytosine methylation, including conditional ablation and transgene-derived overexpression of Nsun2 in the mouse prefrontal cortex (PFC). Neuronal Nsun2-deficiency was associated with a decrease in tRNA m5C levels, resulting in deficits in expression of 70% of tRNAGly isodecoders. Altogether, 1488/5820 proteins changed upon neuronal Nsun2-deficiency, in conjunction with glycine codon-specific defects in translational efficiencies. Loss of Gly-rich proteins critical for glutamatergic neurotransmission was associated with impaired synaptic signaling at PFC pyramidal neurons and defective contextual fear memory. Changes in the neuronal translatome were also associated with a 146% increase in glycine biosynthesis. These findings highlight the methylation sensitivity of glycinergic tRNAs in the adult PFC. Furthermore, they link synaptic plasticity and complex behaviors to epitranscriptomic modifications of cognate tRNAs and the proteomic homeostasis associated with specific amino acids., The link between tRNA modifications, protein translation, and behavior is unclear. Here, the authors show that neuronal Nsun2 deficiency results in codon-specific epitranscriptomic changes of Gly-tRNAs and proteomic changes affecting synaptic signaling and behavior in mice.

Through the combination of heterocyclic thiones with variation in the identity of the heterocyclic elements, namely, imidazolidine-2-thione, 2-mercaptobenzimidazole, 2-mercapto-5-methylbenzimidazole, 2-mercaptobenzoxazole, and 2-mercaptobenzothiazole with the common halogen-bond donors 1,2-, 1,3-, and 1,4-diiodotetrafluorobenzene, 1,3,5-trifluorotriiodobenzene, and tetraiodoethylene, a series of 18 new crystalline structures were characterized. In most cases, N—H...S hydrogen bonding was observed, with these interactions in imidazole-containing structures typically resulting in two-dimensional motifs (i.e. ribbons). Lacking the second N—H group, the thiazole and oxazole hydrogen bonding resulted in only dimeric pairs. C—I...S and C—I...I halogen bonding, as well as C=S...I chalcogen bonding, served to consolidate the packing by linking the hydrogen-bonding ribbons or dimeric pairs.

Memory-updating is critical in dynamic environments because updating memories with new information promotes versatility. However, little is known about how memories are updated with new information. To study how neuronal ensembles might support memory-updating, we used a hippocampus-dependent spatial reversal task to measure hippocampal ensemble dynamics when mice switched navigational goals. Using Miniscope calcium imaging, we identified neuronal ensembles (co-active neurons) in dorsal CA1 that were spatially tuned and stable across training sessions. When reward locations were moved during a reversal session, a subset of these ensembles decreased their activation strength, correlating with memory-updating. These “remodeling” ensembles were a result of weakly-connected neurons becoming less co-active with their peers. Middle-aged mice were impaired in reversal learning, and the prevalence of their remodeling ensembles correlated with their memory-updating performance. Therefore, we have identified a mechanism where the hippocampus breaks down ensembles to support memory-updating.

A new polymorph of N-tert-butyl-2-thioimidazole (1), along with its cocrystals with 1,4-diiodotetrafluorobenzene (2), tetraiodoethylene (3), and molecular iodine (4) have been synthesized. Compound 1 is a new polymorph of a previously reported structure. A series of noncovalent N–H⋯S, N–H⋯I, and I⋯S interactions all contribute to the packing. In 1–3, a pair of N–H⋯S contributes to the formation of imidazole dimers, a commonly observed motif for these systems, which are then linked together through C–I⋯S halogen bonding. This halogen bond occurs approximately normal to the imidazole ring plane. In 4, the addition of I2 to the sulfur atom interrupts N–H⋯S dimer formation, with the primary interactions between neighboring imidazole molecules being of the N–H⋯I and C=S⋯I. This variety of intermolecular interactions leads to the formation of double-stranded chains, ribbons, and sheets. A new polymorph of N-tert-butyl-2-thioimidazole, along with its cocrystals with 1,4-diiodotetrafluorobenzene, tetraiodoethylene, and molecular iodine have been synthesized. A series of noncovalent N–H⋯S, N–H⋯I, and I⋯S all contribute to the packing

A series of cocrystals of Ph3 P=E (E=O, S, Se) with organoiodines were studied to understand the roles of noncovalent interactions including chalcogen (ChB) and halogen (XB) bonding in their formation. The structure of the cocrystal of Ph3 P=S and 1,2-diiodotetrafluorobezene was determined, which demonstrates a similar chalcogen⋅⋅⋅iodine XB pattern to the previously reported isomorphic Ph3 P=Se structure. The cocrystalline structures resulting from the combination of 1,3-diiodotetrafluorobenzene (1,3-F4 DIB), as well as iodopentafluorobenzene, with all three triphenylphosphine chalcogenides, were also determined. The (Ph3 P=Se) ⋅ (1,3-F4 DIB) cocrystal presents a rare example of a selenium⋅⋅⋅organoiodine ChB. The observed ChB and XB interactions have normalized distance parameters (RXB ) ranging from 0.80 to 0.98. The strength of the XB and ChB interactions were analyzed using natural bond orbital (NBO) theory, with calculated energies falling between 3.14 kcal/mol and 12.81 kcal/mol.

To study the role of the triiodide (I3 )- anion in establishing various halogen bonding patterns, the trimethylphenylammonium iodide (NMe3 PhI) salt was reacted with diiodine (I2 ) in the presence of a series of organoiodines, tetraiodoethylene (TIE), 1,2-diiodo-3,4,5,6-tetrafluorobenzene (o-F4 DIB), 1,4-diiodo-2,3,5,6-tetrafluorobenzene (p-F4 DIB), and 1,3,5-trifluoro-2,4,6-triiodobenzene (1,3,5-F3 I3 B) to form cocrystals of the organoiodines with the trimethylphenylammonium triiodide (NMe3 PhI3 ) salt. Single-crystal X-ray crystallography revealed the (I3 )- anion served as a halogen bond acceptor for the organoiodine donors, forming a variety of 1-D, 2-D, and 3-D packing arrangements through I⋅⋅⋅I halogen bonding. Significant asymmetry was observed within the (I3 )- anion. The melting points of the cocrystalline materials, as determined by simultaneous DSC/TGA, ranged from 43 °C to 119 °C and showed a strong dependence on the identity of the organoiodine incorporated into the crystal lattice.

Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice., Trauma can cause dysfunctional fear regulation leading some people to develop disorders, such as post-traumatic stress disorder (PTSD). The amygdala regulates fear, whereas PACAP (pituitary adenylate activating peptide) and PAC1 receptors are linked to PTSD symptom severity at genetic/epigenetic levels, with a strong link in females with PTSD. We discovered a PACAPergic projection from the basomedial amygdala (BMA) to the medial intercalated cells (mICCs) in adult mice. In vivo optogenetic stimulation of this pathway increased CFOS expression in mICCs, decreased fear recall, and increased fear extinction. Selective deletion of PAC1 receptors from the mICCs in females reduced fear acquisition, but enhanced fear generalization and reduced fear extinction in males. Optogenetic stimulation of the BMA-mICC PACAPergic pathway produced EPSCs in mICC neurons, which were enhanced by the PAC1 receptor antagonist, PACAP 6-38. Our findings show that mICCs modulate contextual fear in a dynamic and sex-dependent manner via a microcircuit containing the BMA and mICCs, and in a manner that was dependent on behavioral state. SIGNIFICANCE STATEMENT Traumatic stress can affect different aspects of fear behaviors, including fear learning, generalization of learned fear to novel contexts, how the fear of the original context is recalled, and how fear is reduced over time. While the amygdala has been studied for its role in regulation of different aspects of fear, the molecular circuitry of this structure is quite complex. In addition, aspects of fear can be modulated differently in males and females. Our findings show that a specific circuitry containing the neuropeptide PACAP and its receptor, PAC1, regulates various aspects of fear, including acquisition, generalization, recall, and extinction in a sexually dimorphic manner, characterizing a novel pathway that modulates traumatic fear.

Reaction of methylhydrazine with 1,3- and 1,4-diiodotetrafluorobenzene produced cocrystals with the oxidation product sym-hexahydro-1,4-dimethyltetrazine. In contrast, reaction of 1,1-dimethylhydrazine with 1,2-, 1,3-, and 1,4-diiodotetrafluorobenzene, as well as 1,3,5-triiodotrifluorobenzene, yielded cocrystals with tetramethylammonium iodide (NMe4I), via C–I bond scission. For each of the NMe4I cocrystals, different polymoprhs or cocrystal stoichiometries were obtained via the C–I bond scission route, than were obtained by direct reaction of the halobenzene and NMe4I by standard solution techniques.

A series of co-crystallization experiments were performed using 1,4-dibromo- and 1,4-diiodotetrafluorobenzene (Br2F4bz and I2F4bz), as well as 4,4′-dibromo- and 4,4′-diiodooctafluorobiphenyl (Br2F8bph and I2F8bph), with nine N-heterocyclic diamines and the bicyclic, tertiary diamine 1,4-diazabicyclo[2.2.2]octane to elucidate trends between benzene and biphenyl-based halogen bond donors, as well as factors influencing the resulting halogen bond strength. The acceptors chosen contain nitrogen atom geometries resulting in the formation of chains and a total of 29 new crystal structures were obtained. In the majority of cases, cocrystals resulting from Br2F4bz and I2F4bz are isomorphous, as are the structures from Br2F8bph and I2F8bph, but the observed structures are different for benzene versus biphenyl based derivatives. Analysis of the halogen bond geometries indicates statistically significant correlations between halogen bond distance and both molecular electrostatic potential as well as percent buried volume, a measure of the steric encumbrance of the acceptor nitrogen atoms.

Three new cocrystals of bis(diphenylphosphino)ethane (dppe) and p-diiodotetrafluorobenzene (p-F4DIB) were studied using single-crystal X-ray crystallography. Two polymorphs containing a 1:1 dppe:p-...

The role of hydrogen bonding in the crystal packing of a series of 4-aminoperfluoropyridines was studied using single-crystal X-ray crystallography. The aminoperfluoropyridines were synthesized usi...

Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing.

Despite the large comorbidity between PTSD and opioid use disorders, as well as the common treatment of physical injuries resulting from trauma with opioids, the ability of opioid treatments to subsequently modify PTSD-related behavior has not been well studied. Using the stress-enhanced fear learning (SEFL) model for PTSD, we characterized the impact of chronic opioid regimens on the sensitization of fear learning seen following traumatic stress in mice. We demonstrate for the first time that chronic opioid pretreatment is able to robustly augment associative fear learning. Highlighting aversive learning as the cognitive process mediating this behavioral outcome, these changes were observed after a considerable period of drug cessation, generalized to learning about multiple aversive stimuli, were not due to changes in stimulus sensitivity or basal anxiety, and correlated with a marker of synaptic plasticity within the basolateral amygdala. Additionally, these changes were not observed when opioids were given after the traumatic event. Moreover, we found that neither reducing the frequency of opioid administration nor bidirectional manipulation of acute withdrawal impacted the subsequent enhancement in fear learning seen. Given the fundamental role of associative fear learning in the generation and progression of PTSD, these findings are of direct translational relevance to the comorbidity between opioid dependence and PTSD, and they are also pertinent to the use of opioids for treating pain resulting from traumas involving physical injuries.

Tracking animal behavior by video is one of the most common tasks in neuroscience. Previously, we have validated ezTrack, a free, flexible, and easy-to-use software for the analysis of animal behavior. ezTrack's Location Tracking Module can be used for the positional analysis of an individual animal and is applicable to a wide range of behavioral tasks. Separately, ezTrack's Freeze Analysis Module is designed for the analysis of defensive freezing behavior. ezTrack supports a range of desirable tools, including options for cropping and masking portions of the field of view, defining regions of interest, producing summary data for specified portions of time, algorithms to remove the influence of electrophysiology cables and other tethers, batch processing of multiple videos, and video down-sampling. Moreover, ezTrack produces a range of interactive plots and visualizations to promote users' confidence in their results. In this protocols paper, we provide step-by-step instructions for the use of ezTrack, from tips for recording behavior to instructions for using the software for video analysis. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Software environment installation Basic Protocol 2: Using the Location Tracking Module Basic Protocol 3: Using the Freeze Analysis Module.

While research into deep eutectic solvents (DESs) has expanded over the previous two decades, the focus has remained on the utilization of hydrogen bond donors in these systems. Additionally, the majority of the known DESs rely on at least one ionic component. Through the combination of 1,3-dithiane and 1,2-diiodo-3,4,5,6-tetrafluorobenzene (1,2-F4 DIB), we report the first known DES based on halogen bonding. This mixture remains a liquid, with a eutectic melting temperature of 13.7 °C over a range of 1,3-dithiane mole fraction (0.35 to 0.75). Additionally, cocrystals of 1,3- and 1,4-dithiane with 1,2-, 1,3-, and 1,4-F4 DIB, as well as 1,3,5-trifluoro-2,4,6-triiodobenzene were studied via single-crystal X-ray diffraction. These data reveal a wide range of halogen bonding strengths (0.85

Through variations in reaction solvent and stoichiometry, a series of S-diiodine adducts of 1,3- and 1,4-dithiane were isolated by direct reaction of the dithianes with molecular diiodine in solution. In the case of 1,3-dithiane, variations in reaction solvent yielded both the equatorial and the axial isomers of S-diiodo-1,3-dithiane, and their solution thermodynamics were further studied via DFT. Additionally, S,S’-bis(diiodo)-1,3-dithiane was also isolated. The 1:1 cocrystal, (1,4-dithiane)·(I2) was further isolated, as well as a new polymorph of S,S’-bis(diiodo)-1,4-dithiane. Each structure showed significant S···I halogen and chalcogen bonding interactions. Further, the product of the diiodine-promoted oxidative addition of acetone to 1,4-dithiane, as well as two new cocrystals of 1,4-dithiane-1,4-dioxide involving hydronium, bromide, and tribromide ions, was isolated.

Surgical treatment of patients with massive rotator cuff tears is unpredictable because of a low healing rate and high incidence of clinical failure. Arthroscopic superior capsular reconstruction has emerged as a promising technique in treating younger, active patients with massive irreparable rotator cuff tears. Superior capsular insufficiency has been theorized to be a factor in the higher failure rate for repairs of massive tears, and there have been proposals of superior capsular repair in addition to rotator cuff repair to facilitate better healing of massive rotator cuff tears. This article presents our technique of functional rotator cuff augmentation, which is concomitant superior capsular reconstruction with arthroscopic rotator cuff repair, to treat massive, atrophic rotator cuff tears. This technique is used in patients with massive rotator cuff tears and superior capsular insufficiency.

In the course of our ongoing study of halogen bonding in cocrystals of organoiodine molecules with triiodide salts, we have isolated three of the four known polymorphs of triphenylmethylphosphonium triiodide (PPh3MeI3) and found that one of the tetramorphs exhibits a low temperature phase transition not previously described in the literature. Variable temperature crystallographic studies coupled with differential scanning calorimetry were used to determine the transition temperature and solid-state single crystal to single crystal reversibility of the phase change. To monitor the effect of the size of the anion, bromine was introduced to the reaction mixtures to produce trihalide salts (PPh3MeX3) having varying degrees of mixed iodine and bromine content. The resulting modification of anion size led to structural perturbations beyond those previously observed for the PPh3MeI3 polymorphs, giving three different structure types with similar but not identical packing arrangements of the ions. In addition to providing insight into the effect of subtle changes to crystal packing, the mixed trihalides offer structural and electronic tuning to the applicability of rod-shaped trihalides and functional halogen bonding acceptors.

Miniature microscopes have gained considerable traction for in vivo calcium imaging in freely behaving animals. However, extracting calcium signals from raw videos is a computationally complex problem and remains a bottleneck for many researchers utilizing single-photon in vivo calcium imaging. Despite the existence of many powerful analysis packages designed to detect and extract calcium dynamics, most have either key parameters that are hard-coded or insufficient step-by-step guidance and validations to help the users choose the best parameters. This makes it difficult to know whether the output is reliable and meets the assumptions necessary for proper analysis. Moreover, large memory demand is often a constraint for setting up these pipelines since it limits the choice of hardware to specialized computers. Given these difficulties, there is a need for a low memory demand, user-friendly tool offering interactive visualizations of how altering parameters at each step of the analysis affects data output. Our open-source analysis pipeline, Minian (Miniscope Analysis), facilitates the transparency and accessibility of single-photon calcium imaging analysis, permitting users with little computational experience to extract the location of cells and their corresponding calcium traces and deconvolved neural activities. Minian contains interactive visualization tools for every step of the analysis, as well as detailed documentation and tips on parameter exploration. Furthermore, Minian has relatively small memory demands and can be run on a laptop, making it available to labs that do not have access to specialized computational hardware. Minian has been validated to reliably and robustly extract calcium events across different brain regions and from different cell types. In practice, Minian provides an open-source calcium imaging analysis pipeline with user-friendly interactive visualizations to explore parameters and validate results.

Adaptive reward-related decision making requires accurate prospective consideration of the specific outcome of each option and its current desirability. Often this information must be inferred based on the presence of predictive environmental events. The basolateral amygdala (BLA) and medial orbitofrontal cortex (mOFC) are two key nodes in the circuitry supporting such outcome expectations, but very little is known about the function of direct connections between these regions. Here, in male rats, we first anatomically confirmed the existence of bidirectional, direct projections between the mOFC and BLA and found that BLA projections to mOFC are largely distinct from those to lateral OFC (lOFC). Next, using pathway-specific chemogenetic inhibition and the outcome-selective Pavlovian-to-instrumental transfer and devaluation tests, we interrogated the function of the bidirectional mOFC–BLA connections in reward-directed behavior. We found evidence that the mOFC→BLA pathway mediates the use of environmental cues to understand which specific reward is predicted, information needed to infer which action to choose, and how desirable that reward is to ensure adaptive responses to the cue. By contrast, the BLA→mOFC pathway is not needed to use the identity of an expected reward to guide choice but does mediate adaptive responses to cues based on the current desirability of the reward they predict. These functions differ from those we previously identified for the lOFC–BLA circuit. Collectively, the data reveal the mOFC–BLA circuit as critical for the cue-dependent reward outcome expectations that influence adaptive behavior and decision making. SIGNIFICANCE STATEMENT To make good decisions we evaluate how advantageous a particular course of action would be. This requires understanding what rewarding outcomes can be expected and how desirable they currently are. Such prospective considerations are critical for adaptive decision making but disrupted in many psychiatric diseases. Here, we reveal that direct connections between the medial orbitofrontal cortex and basolateral amygdala mediate these functions. These findings are especially important in light of evidence of dysfunction in this circuit in substance use disorder and mental illnesses marked by poor decision making.