Hippocampal Dysfunction in Schizophrenia and Aberrant Hippocampal Synaptic Plasticity in Rodent Model Psychosis: a Selective Review.

Schizophrenia is a complex, heterogeneous psychiatric disorder that affects about 1% of the global population. Hippocampal dysfunction has been linked to both cognitive deficits and positive symptoms in schizophrenia. Here, we briefly review current findings on disrupted hippocampal processing from a clinical perspective before concentrating on preclinical studies of aberrant hippocampal synaptic plasticity using the N-methyl-D-aspartate receptor hypofunction model of psychosis and related findings from genetic models. Taken together, the results put the case for maladaptive hippocampal synaptic plasticity and its extrinsic connections as mechanistic underpinnings of cognitive impairments in schizophrenia.

O avesso do mesmo lugar / El revés del mismo lugar / The reverse of the same place / L'envers du même endroit

Neste artigo, parte-se das experiências de fronteira de dois meninos. Uma é a narrativa de Zain, no filme Cafarnaum, anterior à sua migração do Líbano; a outra, o caso clínico de Túlio, construído por um grupo de supervisão em serviço de medidas socioeducativas em São Paulo. Abordaremos o laço social nesses distintos contextos, observando subjetividades singulares e universais de adolescentes marcados por desigualdade e injustiça social. O objetivo é interrogar a psicanálise diante da condição de desenraizamento imposta ao sujeito na contemporaneidade. O cinema, objeto da cultura, evoca a nossa responsabilidade ética ao aproximar ficção e realidade, denunciando violências de gênero e situações desumanas oferecidas aos imigrantes e às infâncias subalternizadas. Há o convite para a criação de dispositivos clínicos que ofereçam a hospitalidade como operador conceitual diante das urgências sociais

El presente artículo se basa en las experiencias fronterizas de dos niños. Una es la narración de Zain en la película Cafarnaum, antes de su emigración del Líbano; la otra es el caso clínico de Tulio, construido por un grupo de supervisión em un servicio de medidas socioeducativas en São Paulo. Abordaremos el vínculo social en estos diferentes contextos, observando subjetividades singulares y universales de adolescentes marcados por la desigualdad y la injusticia social. El objetivo es cuestionar el psicoanálisis ante la condición de desarraigo que se impone al sujeto en la contemporaneidad. El cine, objeto de la cultura, evoca nuestra responsabilidad ética al unir ficción y realidad, denunciando la violencia de género y las situaciones inhumanas que se ofrecen a los inmigrantes y a las infancias marginadas. Hay una invitación a crear dispositivos clínicos que ofrezcan hospitalidad como operador conceptual ante las urgencias sociales

This article is based on the frontier experiences of two boys. One is Zain's narrative in the movie Cafarnaum, before his emigration from Lebanon; the other is the clinical case of Tulio, developed by a supervision group in a social and educational measures service in São Paulo. We will approach the social bond in those different contexts, observing singular and universal subjectivities in adolescents marked by inequality and social injustice. The goal is to interrogate psychoanalysis in the face of the uprooting condition imposed on contemporaneous subjects. Cinema, an object of culture, evokes our ethical responsibility by bringing fiction and reality together, denouncing gender violence and inhuman situations faced by immigrants and underprivileged children. There is an invitation to create clinical devices that offer hospitality as a conceptual operator in the face of social urgencies

Dans cet article, nous partons des expériences frontalières de deux garçons. L'un est le parcours de Zain dans le film Cafarnaum, avant sa migration du Liban ; dans l'autre, le cas clinique de Tulio, construit par un groupe de supervision d'une institution de protection socio-éducative à São Paulo. Nous aborderons le lien social dans ces différents contextes, en observant les subjectivités singulières et universelles d'adolescents marqués par des inégalités et l'injustice sociale. Il s'agit d'interroger la psychanalyse face à la condition de déracinement imposée au sujet dans le contemporain. Le cinéma, objet de culture, évoque notre responsabilité éthique en proposant la rencontre entre fiction et réalité, en dénonçant la violence de genre et les situations inhumaines imposées aux immigrés et aux enfances subalternes. Il s'agit ici d'une invitation à créer des dispositifs cliniques qui partent de l' hospitalité comme opérateur conceptuel face aux urgences sociales

The validity and reliability of counter movement jump height measured with the Polar Vantage V2 sports watch.

The purpose of the present study was to assess the validity and reliability of the jump height measured by the Polar Vantage V2 sports watch in comparison to a gold-standard force plate measurement. Fifteen healthy adults, seven female, age 20-42 years participated in the study and performed six sets of three CMJs, on two consecutive days. The participants wore the Polar Vantage V2 sports watch (Polar Electro Oy, Kempele, Finland) whilst performing the jumps on two force plates (AMTI, Watertown, Massachusetts, United States). Jump height was on the one hand extracted directly from the watch ("leg recovery test") and on the other hand calculated by the flight time method with the force plate data. To assess validity, we calculated the mean absolute error, constructed Bland-Altman plots and applied an ordinary least squares regression analysis. To test for left-to-right and day-to-day reliability, we calculated Pearson and intraclass correlations. We found a mean error of ≈5% and a high correlation (r = 0.96; p < 0.001) for the jump height measured by the Polar Vantage V2 sports watch compared to the force plate measurement. The Bland-Altmann plot together with the ordinary least squares regression analysis showed no systematic bias between the methods with a minimal difference at a jump height of 30 cm. For reliability of left-to-right and day-to-day measurements, we found high Pearson and ICC correlations and no indications for systematic bias by Bland-Altmann analysis. The present study has demonstrated that the "leg recovery test" of the Polar Vantage V2 sports watch provide a valid and reliable measurement of the mean vertical jump height of three consecutive CMJs. For the first time the jump height of a CMJ can be measured solely by a sports watch without the need to attach additional sensors or measurement devices. Thus, the "leg recovery test" is an easy to administer, valid and reliable test, that can be used in future studies to measure CMJ-height in the field when lab-based assessments are unavailable or inconvenient. This opens new avenues for cross-sectional and longitudinal assessments of neuromuscular power of the lower extremities in a large number of participants.

Unanticipated fake-and-cut maneuvers do not increase knee abduction moments in sport-specific tasks: Implication for ACL injury prevention and risk screening.

Non-contact anterior cruciate ligament injuries typically occur during cutting maneuvers and are associated with high peak knee abduction moments (KAM) within early stance. To screen athletes for injury risk or quantify the efficacy of prevention programs, it may be necessary to design tasks that mimic game situations. Thus, this study compared KAMs and ranking consistency of female handball players in three sport-specific fake-and-cut tasks of increasing complexity. The biomechanics of female handball players (n = 51, mean ± SD: 66.9 ± 7.8 kg, 1.74 ± 0.06 m, 19.2 ± 3.4 years) were recorded with a 3D motion capture system and force plates during three standardized fake-and-cut tasks. Task 1 was designed as a simple pre-planned cut, task 2 included catching a ball before a pre-planned cut in front of a static defender, and task 3 was designed as an unanticipated cut with three dynamic defenders involved. Inverse dynamics were used to calculate peak KAM within the first 100 ms of stance. KAM was decomposed into the frontal plane knee joint moment arm and resultant ground reaction force. RANOVAs (α ≤ 0.05) were used to reveal differences in the KAM magnitudes, moment arm, and resultant ground reaction force for the three tasks. Spearman's rank correlations were calculated to test the ranking consistency of the athletes' KAMs. There was a significant task main effect on KAM (p = 0.02; η p 2 = 0.13). The KAM in the two complex tasks was significantly higher (task 2: 1.73 Nm/kg; task 3: 1.64 Nm/kg) than the KAM in the simplest task (task 1: 1.52 Nm/kg). The ranking of the peak KAM was consistent regardless of the task complexity. Comparing tasks 1 and 2, an increase in KAM resulted from an increased frontal plane moment arm. Comparing tasks 1 and 3, higher KAM in task 3 resulted from an interplay between both moment arm and the resultant ground reaction force. In contrast to previous studies, unanticipated cutting maneuvers did not produce the highest KAMs. These findings indicate that the players have developed an automated sport-specific cutting technique that is utilized in both pre-planned and unanticipated fake-and-cut tasks.

Predicting ACL Injury Using Machine Learning on Data From an Extensive Screening Test Battery of 880 Female Elite Athletes.

BACKGROUND: Injury risk prediction is an emerging field in which more research is needed to recognize the best practices for accurate injury risk assessment. Important issues related to predictive machine learning need to be considered, for example, to avoid overinterpreting the observed prediction performance. PURPOSE: To carefully investigate the predictive potential of multiple predictive machine learning methods on a large set of risk factor data for anterior cruciate ligament (ACL) injury; the proposed approach takes into account the effect of chance and random variations in prediction performance. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: The authors used 3-dimensional motion analysis and physical data collected from 791 female elite handball and soccer players. Four common classifiers were used to predict ACL injuries (n = 60). Area under the receiver operating characteristic curve (AUC-ROC) averaged across 100 cross-validation runs (mean AUC-ROC) was used as a performance metric. Results were confirmed with repeated permutation tests (paired Wilcoxon signed-rank-test; P < .05). Additionally, the effect of the most common class imbalance handling techniques was evaluated. RESULTS: For the best classifier (linear support vector machine), the mean AUC-ROC was 0.63. Regardless of the classifier, the results were significantly better than chance, confirming the predictive ability of the data and methods used. AUC-ROC values varied substantially across repetitions and methods (0.51-0.69). Class imbalance handling did not improve the results. CONCLUSION: The authors' approach and data showed statistically significant predictive ability, indicating that there exists information in this prospective data set that may be valuable for understanding injury causation. However, the predictive ability remained low from the perspective of clinical assessment, suggesting that included variables cannot be used for ACL prediction in practice.

Understanding Bench Press Biomechanics-The Necessity of Measuring Lateral Barbell Forces.

ABSTRACT: Mausehund, L, Werkhausen, A, Bartsch, J, and Krosshaug, T. Understanding bench press biomechanics-The necessity of measuring lateral barbell forces. J Strength Cond Res 36(10): 2685-2695, 2022-The purpose of this study was to advance the expertise of the bench press exercise by complementing electromyographic (EMG) with net joint moment (NJM) and strength normalized NJM (nNJM) measurements, thus establishing the magnitude of the elbow and shoulder muscular loads and efforts. Normalized NJMs were determined as the ratio of the bench press NJMs to the maximum NJMs produced during maximum voluntary isokinetic contractions. Furthermore, we wanted to assess how changes in grip width and elbow positioning affected elbow and shoulder NJMs and nNJMs, and muscle activity of the primary movers. Thirty-five strength-trained adults performed a 6-8 repetition maximum set of each bench press variation, while elbow and shoulder NJMs and EMG activity of 7 upper extremity muscles were recorded. The results show that all bench press variations achieved high elbow and shoulder muscular efforts. A decrease in grip width induced larger elbow NJMs, and larger EMG activity of the lateral head of the triceps brachii, anterior deltoid, and clavicular head of the pectoralis major ( p ≤ 0.05). An increase in grip width elicited larger shoulder NJMs and nNJMs, and larger EMG activity of the abdominal head of the pectoralis major ( p ≤ 0.05). In conclusion, all bench press variations may stimulate strength gains and hypertrophy of the elbow extensors and shoulder flexors and horizontal adductors. However, greater adaptations of the elbow extensors and shoulder flexors may be expected when selecting narrower grip widths, whereas wider grip widths may induce greater adaptations of the shoulder horizontal adductors.

Stress-Induced Enhanced Long-Term Potentiation and Reduced Threshold for N-Methyl-D-Aspartate Receptor- and ß-Adrenergic Receptor-Mediated Synaptic Plasticity in Rodent Ventral Subiculum.

Stress is a biologically relevant signal and can modulate hippocampal synaptic plasticity. The subiculum is the major output station of the hippocampus and serves as a critical hub in the stress response network. However, stress-associated synaptic plasticity in the ventral subiculum has not been adequately addressed. Therefore, we investigated the impact of a single exposure to an inherently stressful two-way active avoidance conditioning on the induction of long-term potentiation (LTP) at CA1-subiculum synapses in ventral hippocampal slices from young adult rats 1 day after stressor exposure. We found that acute stress enhanced LTP and lowered the induction threshold for a late-onset LTP at excitatory CA1 to subicular burst-spiking neuron synapses. This late-onset LTP was dependent on the activation of ß-adrenergic and glutamatergic N-methyl-D-aspartate receptors and independent of D1/D5 dopamine receptor activation. Thereby, we present a cellular mechanism that might contribute to behavioral stress adaptation after acute stressor exposure.

Functional deletion of neuropeptide Y receptors type 2 in local synaptic networks of anteroventral BNST facilitates recall and increases return of fear.

Return of previously extinguished fear memories presents a major hurdle in treatment of fear-related disorders. Neuropeptide Y receptors type 2 (Y2R) in the bed nucleus of stria terminalis (BNST) seem to play a crucial role in modulation of remote fear memories. Here, we targeted Cre-channelrhodopsin-2 to defined subregions of BNST or central amygdala (CeA) in floxed Y2R mice (Y2lox/lox) for functional deletion of Y2R. We combined fear training and behavioral studies in vivo with optogenetic-electrophysiological analysis of BNST synaptic network activity ex vivo, in order to identify regional and cellular specificities of Y2R influence. Deletion of Y2R in the ventral section of anterior BNST (BNSTav) did not affect fear acquisition, but increased conditioned fear during recall and extinction learning, and aggravated remote fear return. By contrast, deletion of Y2R in the dorsal section of anterior BNST (BNSTad) or CeA did not influence acquisition, extinction or return of fear memories. Ex vivo optogenetic-electrophysiological analysis revealed Y2R-expressing local GABAergic inhibitory networks in BNST, both within (intraregional) and in-between (inter-regional) BNST subregions. Stimulation of Y2R resulted in a presynaptically mediated reduction of GABAergic responses, which did not differ between intraregional but predominantly affected inter-regional connections from BNSTav to BNSTad. Moreover, deletion of Y2R decreased the excitation/inhibition balance in BNSTav neurons, suggesting a regulatory influence of endogenous NPY via intraregional GABAergic microcircuits. This study reveals Y2R within local GABAergic networks in BNST as key elements in facilitating extinction and reducing return of remote fear memories, suggesting a potential avenue for translational purposes.

Noncanonical, Dopamine-Dependent Long-Term Potentiation at Hippocampal Output Synapses in a Rodent Model of First-Episode Psychosis.

Cognitive deficits and positive symptoms in schizophrenia have both been linked to hippocampal dysfunction. Recently, subregion-specific aberrant and maladaptive hippocampal synaptic plasticity has been suggested as one of the mechanistic underpinnings. The subiculum is the final output hub of the hippocampus and orchestrates hippocampal information transfer to other brain regions. While most CA1 pyramidal neurons show regular-spiking behavior, subicular output neurons comprise bursting and regular-firing pyramidal cells. These two cell types target different brain regions and express unique forms of synaptic plasticity. Here, we used a single systemic application of the noncompetitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 to model first-episode psychosis in rats and studied long-term potentiation (LTP) in subicular regular-firing cells in acute hippocampal slices. Previously, we have reported a facilitation of a presynaptic, late-onset LTP in subicular bursting pyramidal cells after systemic NMDAR antagonism. Here, we show that single systemic NMDAR antagonist application also facilitates the induction of a noncanonical, but postsynaptic NMDAR-independent LTP in ventral subicular but not in CA1 regular-firing pyramidal cells. This form of LTP was dependent on D1/D5 dopamine receptor activation. Activation of D1/D5 dopamine receptors by a specific agonist mimicked and occluded LTP induced by electrical high-frequency stimulation (HFS). Furthermore, our results indicate that this form of LTP relies on postsynaptic Ca2+ signaling and requires the activation of protein kinase A. Considering the pivotal role of the subiculum as information gatekeeper between the hippocampus and other brain regions, this aberrant LTP in ventral subicular regular-firing neurons is expected to interfere with physiological hippocampal output processing and might thereby contribute to hippocampal dysfunction in psychotic events.

Impaired anandamide/palmitoylethanolamide signaling in hippocampal glutamatergic neurons alters synaptic plasticity, learning, and emotional responses.

Endocannabinoid signaling via anandamide (AEA) is implicated in a variety of neuronal functions and considered a promising therapeutic target for numerous emotion-related disorders. The major AEA degrading enzyme is fatty acid amide hydrolase (FAAH). Genetic deletion and pharmacological inhibition of FAAH reduce anxiety and improve emotional responses and memory in rodents and humans. Complementarily, the mechanisms and impact of decreased AEA signaling remain to be delineated in detail. In the present study, using the Cre/loxP system combined with an adeno-associated virus (AAV)-mediated delivery system, FAAH was selectively overexpressed in hippocampal CA1-CA3 glutamatergic neurons of adult mice. This approach led to specific FAAH overexpression at the postsynaptic site of CA1-CA3 neurons, to increased FAAH enzymatic activity, and, in consequence, to decreased hippocampal levels of AEA and palmitoylethanolamide (PEA), but the levels of the second major endocannabinoid 2-arachidonoyl glycerol (2-AG) and of oleoylethanolamide (OEA) were unchanged. Electrophysiological recordings revealed an enhancement of both excitatory and inhibitory synaptic activity and of long-term potentiation (LTP). In contrast, excitatory and inhibitory long-term depression (LTD) and short-term synaptic plasticity, apparent as depolarization-induced suppression of excitation (DSE) and inhibition (DSI), remained unaltered. These changes in hippocampal synaptic activity were associated with an increase in anxiety-like behavior, and a deficit in object recognition memory and in extinction of aversive memory. This study indicates that AEA is not involved in hippocampal short-term plasticity, or eLTD and iLTD, but modulates glutamatergic transmission most likely via presynaptic sites, and that disturbances in this process impair learning and emotional responses.

Physiological Profile of Neuropeptide Y-Expressing Neurons in Bed Nucleus of Stria Terminalis in Mice: State of High Excitability.

Both, the anterior bed nucleus of the stria terminalis (BNST) and the neuropeptide Y (NPY) system are involved in shaping fear and defensive responses that adapt the organism to potentially life-threatening conditions. NPY is expressed in the BNST but NPY-expressing neurons in this critical hub in the stress response network have not been addressed before. Therefore, we performed whole-cell patch-clamp recordings in acute slices of anterior BNST from Npy-hrGFP transgenic mice to identify and characterize NPY-expressing neurons. We show that NPY-positive and NPY-negative neurons in anterior BNST match the previous classification scheme of type I (Regular Spiking), type II (Low-Threshold Bursting), and type III (fast Inward Rectifying) cells, although the proportion of these physiological phenotypes was similar within both neuronal subpopulations. However, NPY-positive and NPY-negative neurons possessed distinct intrinsic electrophysiological properties. NPY-positive neurons displayed higher input resistance and lower membrane capacitance, corresponding to small cell bodies and shorter less ramified dendrites, as compared to their NPY-negative counterparts. Furthermore, NPY-positive neurons generated higher frequent series of action potentials upon membrane depolarization and displayed significantly lower GABAA receptor-mediated synaptic responsiveness during evoked, spontaneous, and elementary synaptic activity. Taken together, these properties indicate an overall state of high excitability in NPY-positive neurons in anterior BNST. In view of the role of the anterior BNST in anxiety- and stress-related behaviors, these findings suggest a scenario where NPY-positive neurons are preferentially active and responsive to afferent inputs, thereby contributing to adaptation of the organism to stressful environmental encounters.

Epiretinal membrane as a source of errors during the measurement of peripapillary nerve fibre thickness using spectral-domain optical coherence tomography (SD-OCT).

PURPOSE: We aimed to examine the extent to which measurement errors in the determination of retinal nerve fibre layer (RNFL) using spectral-domain optical coherence tomography (SD-OCT) occur in cases of epiretinal membrane and whether systematic deviations are found in the values obtained. METHODS: A macular scan and a circumpapillary scan were performed on 97 eyes of 97 patients using SD-OCT. Group 1 comprised 53 patients with epiretinal membrane at an age of 70 ± 4.8 years (median ± average absolute deviation). Group 2 consisted of 44 patients without any macular pathologies (median age 70 ± 5.8 years). Differences in the thickness of the RNFL and segmentation errors in the detection of the RNFL were recorded quantitatively in both groups and checked for statistical significance using non-parametric tests. RESULTS: The median central retinal thickness in Group 1 was 357 ± 79 µm (median ± average absolute deviation), and in Group 2 it was 270 ± 11 µm (p < 0.001). The result of the quadrant-by-quadrant measurement of the average RNFL in Group 1 and Group 2, respectively, was: temporal 88 ± 17 and 73 ± 9 µm, inferior 121 ± 17 and 118 ± 15 µm, nasal 87 ± 15 and 89 ± 14 µm and superior 115 ± 15 and 114 ± 9 µm. Temporally, the difference was statistically significant (p < 0.001). Segmentation errors of the RNFL were found in 19 of 53 eyes (35.8 %) in Group 1 and in no eyes (p < 0.001) in Group 2. CONCLUSIONS: In eyes with epiretinal membrane, measuring errors in the SD-OCT occur significantly more frequently than in eyes without any retinal pathologies. If epiretinal membrane and glaucoma are present simultaneously, the results of the automated RNFL measurement using SD-OCT should be critically scrutinised, even if no papillary changes are visible clinically.

Enhanced dopamine-dependent hippocampal plasticity after single MK-801 application.

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca(2+) channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.

High-frequency stimulation of the temporoammonic pathway induces input-specific long-term potentiation in subicular bursting cells.

The subiculum (Sub) as a part of the hippocampal formation is thought to play a functional role in learning and memory. In addition to its major input from CA1 pyramidal cells, the subiculum receives input from the entorhinal cortex (EC) via the temporoammonic pathway. Thus far, synaptic plasticity in the subiculum was mainly investigated at CA1-Sub synapses. According to their spiking pattern, pyramidal cells in the subiculum were classified as bursting cells and non-bursting cells. In the present study, we demonstrate that subicular bursting cells show input-specific forms of long-term potentiation (LTP). At CA1-Sub synapses, bursting cells have been shown to express a presynaptic NMDA receptor-dependent LTP that depends on the activation of a cAMP-PKA cascade (Wozny et al., Journal of Physiology 2008). In contrast, at EC-Sub synapses the induction of LTP in bursting cells shows a high induction-threshold and relies on the activation of postsynaptic NMDA receptors, postsynaptic depolarization and postsynaptic Ca(2+) influx. Each form of LTP is input-specific and fails to induce heterosynaptic plasticity. Taken together, our data suggest that distinct, input-specific mechanisms govern high frequency-induced LTP at subicular bursting cells' synapses.

Activation of dopamine D1/D5 receptors facilitates the induction of presynaptic long-term potentiation at hippocampal output synapses.

Encoding of novel information has been proposed to rely on the time-locked release of dopamine in the hippocampal formation during novelty detection. However, the site of novelty detection in the hippocampus remains a matter of debate. According to current models, the CA1 and the subiculum act as detectors and distributors of novel sensory information. Although most CA1 pyramidal neurons exhibit regular-spiking behavior, the majority of subicular pyramidal neurons fire high-frequency bursts of action potentials. The present study investigates the efficacy of dopamine D1/D5 receptor activation to facilitate the induction of activity-dependent long-term potentiation (LTP) in rat CA1 regular-spiking and subicular burst-spiking pyramidal cells. Using a weak stimulation protocol, set at a level subthreshold for the induction of LTP, we show that activation of D1/D5 receptors for 5-10 min facilitates LTP in subicular burst-spiking neurons but not in CA1 neurons. The results demonstrate that D1/D5 receptor-facilitated LTP is NMDA receptor-dependent, and requires the activation of protein kinase A. In addition, the D1/D5 receptor-facilitated LTP is shown to be presynaptically expressed and relies on presynaptic Ca(2+) signaling. The phenomenon of dopamine-induced facilitation of presynaptic NMDA receptor-dependent LTP in subicular burst-spiking pyramidal cells is in accordance with observations of the time-locked release of dopamine during novelty detection in this brain region, and reveals an intriguing mechanism for the encoding of hippocampal output information.