Sensory experiences and learning induce long-lasting changes in both excitatory and inhibitory synapses, thereby providing a crucial substrate for memory. However, the co-tuning of excitatory long-term potentiation (eLTP) or depression (eLTD) with the simultaneous changes at inhibitory synapses (iLTP/iLTD) remains unclear. Herein, we investigated the co-expression of NMDA-induced synaptic plasticity at excitatory and inhibitory synapses in hippocampal CA1 pyramidal cells (PCs) using a combination of electrophysiological, optogenetic, and pharmacological approaches. We found that inhibitory inputs from somatostatin (SST) and parvalbumin (PV)-positive interneurons onto CA1 PCs display input-specific long-term plastic changes following transient NMDA receptor activation. Notably, synapses from SST-positive interneurons consistently exhibited iLTP, irrespective of the direction of excitatory plasticity, whereas synapses from PV-positive interneurons predominantly showed iLTP concurrent with eLTP, rather than eLTD. As neuroplasticity is known to depend on the extracellular matrix, we tested the impact of metalloproteinases (MMP) inhibition. MMP3 blockade interfered with GABAergic plasticity for all inhibitory inputs, whereas MMP9 inhibition selectively blocked eLTP and iLTP in SST-CA1PC synapses co-occurring with eLTP but not eLTD. These findings demonstrate the dissociation of excitatory and inhibitory plasticity co-expression. We propose that these mechanisms of plasticity co-expression may be involved in maintaining excitation-inhibition balance and modulating neuronal integration modes.

The resistance of Helicobacter pylori (H. pylori) has increased in recent years, prompting a trend in the research and development of new drugs. In our study, three derivatives (JF-1, JF-2, and JF-3) were synthesized using 6-gingerol as the main component, while JF-4, containing both 6-gingerol and 6-shogaol as the main components, was extracted from dried ginger. The minimum inhibitory concentrations (MICs), determined using the ratio dilution method, were 80 μg/mL for JF-1, 40 μg/mL for JF-2, 30 μg/mL for JF-3, 40 μg/mL for JF-4, 60 μg/mL for 6-gingerol standard (SS), and 0.03 μg/mL for amoxicillin (AMX). After treating H. pylori-infected mice, the inflammation of the gastric mucosa was suppressed. The eradication rate of H. pylori was 16.7% of JF-3 low-dose treatment (LDT), 25.0% of JF-3 high-dose treatment (HDT), 16.7% of JF-4 LDT, 16.7% of JF-4 HDT, 30% of SS LDT, 50% of SS HDT, and 36.4% of the positive control group (PCG). The levels of gastrin, somatostatin (SST), IFN-γ, IL-4, and IL-8 were significantly recovered in the JF-3 and JF-4 administration groups, but the effect was stronger in the high-dose group. These results demonstrate that 6-gingerol and its derivatives have significant anti-Helicobacter pylori effects and are promising potential treatments for H. pylori infection.

Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 (p = 0.024, r = 0.49) and E-Cadherin (p = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 (p = 0.107, r = -0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.

Aging-related biochemical changes in nerve cells lead to dysfunctional synapses and disrupted neuronal circuits, ultimately affecting vital processes such as brain plasticity, learning, and memory. The imbalance between excitation and inhibition in synaptic function during aging contributes to cognitive impairment, emphasizing the importance of compensatory mechanisms. Fear conditioning-related plasticity of the somatosensory barrel cortex, relying on the proper functioning and extensive up regulation of the GABAergic system, in particular interneurons containing somatostatin, is compromised in aging (one-year-old) mice. The present research explores two potential interventions, taurine supplementation, and environmental enrichment, revealing their effectiveness in supporting learning-induced plasticity in the aging mouse brain. They do not act through a mechanism normalizing the Glutamate/GABA balance that is disrupted in aging. Still, they allow for increased somatostatin levels, an effect observed in young animals after learning. These findings highlight the potential of lifestyle interventions and diet supplementation to mitigate age-related cognitive decline by promoting experience-dependent plasticity.

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR2) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin\'s N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR2. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.

Adaptive regulation of feeding depends on linkage of internal states and food outcomes with contextual cues. Human brain imaging has identified dysregulation of a hippocampal-lateral hypothalamic area (LHA) network in binge eating, but mechanistic instantiation of underlying cell-types and circuitry is lacking. Here, we identify an evolutionary conserved and discrete Prodynorphin (Pdyn)-expressing subpopulation of Somatostatin (Sst)-expressing inhibitory neurons in the dorsolateral septum (DLS) that receives primarily dorsal, but not ventral, hippocampal inputs. DLS(Pdyn) neurons inhibit LHA GABAergic neurons and confer context- and internal state-dependent calibration of feeding. Viral deletion of Pdyn in the DLS mimicked effects seen with optogenetic silencing of DLS Pdyn INs, suggesting a potential role for DYNORPHIN-KAPPA OPIOID RECEPTOR signaling in contextual regulation of food-seeking. Together, our findings illustrate how the dorsal hippocampus has evolved to recruit an ancient LHA feeding circuit module through Pdyn DLS inhibitory neurons to link contextual information with regulation of food consumption.

OBJECTIVE: This study aimed to evaluate the effectiveness of somatostatin analogues (SA) for cystoid maculopathy (CM) in retinitis pigmentosa (RP) patients.
METHODS: In this retrospective case series, clinical and imaging characteristics of 28 RP patients with CM, unresponsive to carbonic anhydrase inhibitors, were collected from medical charts. All patients received SA treatment as an alternative (octreotide long-acting release at 20 mg/month or 30 mg/month, or lanreotide at 90 mg/month or 120 mg/month). Outcome measures were mean reduction in foveal thickness (FT) and foveal volume (FV) and mean increase in best-corrected visual acuity at 3, 6 and 12 months of treatment initiation. Linear mixed models were used to calculate the effectiveness over time.
RESULTS: 52 eyes of 28 RP patients were included; 39% were male. The median age at the start of treatment was 39 years (IQR 30-53). Median follow-up was 12 months (range 6-12). From baseline to 12 months, the mean FT decreased from 409±136 µm to 334±119 µm and the mean FV decreased from 0.31±0.10 mm3 to 0.25±0.04 mm3. Linear mixed model analyses showed a significant decrease in log FT and log FV at 3, 6 and 12 months after the start of treatment compared with baseline measurements (p<0.001, p<0.001, p<0.001). Mean best-corrected visual acuity did not increase significantly (0.46±0.35 logMAR to 0.45±0.38 logMAR after 12 months).
CONCLUSIONS: SA may be an effective alternative treatment to reduce CM in RP patients.

We provide a brief (and unabashedly biased) overview of the pre-transcriptomic history of somatostatin interneuron taxonomy, followed by a chronological summary of the large-scale, NIH-supported effort over the last ten years to generate a comprehensive, single-cell RNA-seq-based taxonomy of cortical neurons. Focusing on somatostatin interneurons, we present the perspective of experimental neuroscientists trying to incorporate the new classification schemes into their own research while struggling to keep up with the ever-increasing number of proposed cell types, which seems to double every two years. We suggest that for experimental analysis, the most useful taxonomic level is the subdivision of somatostatin interneurons into ten or so \"supertypes,\" which closely agrees with their more traditional classification by morphological, electrophysiological and neurochemical features. We argue that finer subdivisions (\"t-types\" or \"clusters\"), based on slight variations in gene expression profiles but lacking clear phenotypic differences, are less useful to researchers and may actually defeat the purpose of classifying neurons to begin with. We end by stressing the need for generating novel tools (mouse lines, viral vectors) for genetically targeting distinct supertypes for expression of fluorescent reporters, calcium sensors and excitatory or inhibitory opsins, allowing neuroscientists to chart the input and output synaptic connections of each proposed subtype, reveal the position they occupy in the cortical network and examine experimentally their roles in sensorimotor behaviors and cognitive brain functions.

BACKGROUND: Carcinoid tumors are rare neuroendocrine malignancies presenting in an increasing number in our center. The incidence of carcinoid tumors is approximatively between 2.5 and 5 cases per 100,000 people of whom about 50% develop carcinoid syndrome. Once the carcinoid syndrome has developed, a carcinoid cardiomyopathy can occur. Carcinoid heart disease (CaHD) remains a serious and rare complication associated with a significant increase in morbidity and mortality. Although carcinoid tumors have been known and studied for several years, there are still scarce data on the anesthetic management and the peri operative period.
METHODS: We describe a case of a Caucasian 44-year-old woman with an unusual presentation of left CaHD with an ileal neuroendocrine tumor and liver metastases. Our preoperative somatostatin administration protocol, limit the cardiac damage. The maintenance of stable hemodynamics, the use of balanced anesthetic technique, all along with a good understanding of the pathology, played a major role in the successful management of anesthesia. This case report allows us to introduce our decision algorithm for the management of this type of pathology in our tertiary hospital, Cliniques Universitaires Saint-Luc.
CONCLUSIONS: Despite the paucity of data, anesthetic management of patients with carcinoid tumor can be safely performed with effective hemodynamic monitoring and a good understanding of the pathophysiology. Knowledge and application of a clear institutional algorithm for octreotide administration and multidisciplinary consultation at a referral center are essential for the management of these patients.

The integration of spatial information in the mammalian dentate gyrus (DG) is critical to navigation. Indeed, DG granule cells (DGCs) rely upon finely balanced inhibitory neurotransmission in order to respond appropriately to specific spatial inputs. This inhibition arises from a heterogeneous population of local GABAergic interneurons (INs) that activate both fast, ionotropic GABAA receptors (GABAAR) and slow, metabotropic GABAB receptors (GABABR), respectively. GABABRs in turn inhibit pre- and postsynaptic neuronal compartments via temporally long-lasting G-protein-dependent mechanisms. The relative contribution of each IN subtype to network level GABABR signal setting remains unknown. However, within the DG, the somatostatin (SSt) expressing IN subtype is considered crucial in coordinating appropriate feedback inhibition on to DGCs. Therefore, we virally delivered channelrhodopsin 2 to the DG in order to obtain control of this specific SSt IN subpopulation in male and female adult mice. Using a combination of optogenetic activation and pharmacology, we show that SSt INs strongly recruit postsynaptic GABABRs to drive greater inhibition in DGCs than GABAARs at physiological membrane potentials. Furthermore, we show that in the adult mouse DG, postsynaptic GABABR signaling is predominantly regulated by neuronal GABA uptake and less so by astrocytic mechanisms. Finally, we confirm that activation of SSt INs can also recruit presynaptic GABABRs, as has been shown in neocortical circuits. Together, these data reveal that GABABR signaling allows SSt INs to control DG activity and may constitute a key mechanism for gating spatial information flow within hippocampal circuits.