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Rodent behavioral analysis is a major specialization in experimental psychology and behavioral neuroscience. Rodents display a wide range of species-specific behaviors, not only in their natural habitats but also under behavioral testing in controlled laboratory conditions. Detecting and categorizing these different kinds of behavior in a consistent way is a challenging task. Observing and analyzing rodent behaviors manually limits the reproducibility and replicability of the analyses due to potentially low inter-rater reliability. The advancement and accessibility of object tracking and pose estimation technologies led to several open-source artificial intelligence (AI) tools that utilize various algorithms for rodent behavioral analysis. These software provide high consistency compared to manual methods, and offer more flexibility than commercial systems by allowing custom-purpose modifications for specific research needs. Open-source software reviewed in this paper offer automated or semi-automated methods for detecting and categorizing rodent behaviors by using hand-coded heuristics, machine learning, or neural networks. The underlying algorithms show key differences in their internal dynamics, interfaces, user-friendliness, and the variety of their outputs. This work reviews the algorithms, capability, functionality, features and software properties of open-source behavioral analysis tools, and discusses how this emergent technology facilitates behavioral quantification in rodent research.

Environmental enrichment (EE) in rodents is associated with a wide range of physiological, affective, and cognitive benefits. A seemingly opposite housing condition, social isolation (SI), is used as a rodent model of stress, negatively affecting several neurobiological mechanisms and hampering cognitive performance. Experimental designs that involve switching between these housing conditions produced mixed results. We evaluated different behavioral and cognitive effects of brief EE following long-term, SI-induced stress. We revealed the influence of enrichment after 30 days of isolation on behavioral despair, anxiety-like behavior, and spatial working memory in adult male Wistar rats and found a substantial anxiolytic effect in the experimental (SI to EE) group. Interestingly, rats exposed to EE also showed increased behavioral despair compared with the control (continuous SI) group. There was no difference in spatial working memory performance at the end of a 5-day water Y-maze (WYM) test. However, the SI to EE animals displayed better memory performance in the first 2 days of the WYM, indicating faster learning. In line with this difference, we recorded significantly more c-Fos-immunopositive (c-Fos+) cells in the retrosplenial and perirhinal cortices of the SI to EE animals. The lateral and basolateral nuclei of the amygdala showed no such difference. These results suggest that brief enrichment following isolation stress leads to differential results in affective and cognitive systems.

Behavioral testing constitutes the primary method to measure the emotional states of nonhuman animals in preclinical research. Emerging as the characteristic tool of the behaviorist school of psychology, behavioral testing of animals, particularly rodents, is employed to understand the complex cognitive and affective symptoms of neuropsychiatric disorders. Following the symptom-based diagnosis model of the DSM, rodent models and tests of depression and anxiety focus on behavioral patterns that resemble the superficial symptoms of these disorders. While these practices provided researchers with a platform to screen novel antidepressant and anxiolytic drug candidates, their construct validity—involving relevant underlying mechanisms—has been questioned. In this review, we present the laboratory procedures used to assess depressive- and anxiety-like behaviors in rats and mice. These include constructs that rely on stress-triggered responses, such as behavioral despair, and those that emerge with nonaversive training, such as cognitive bias. We describe the specific behavioral tests that are used to assess these constructs and discuss the criticisms on their theoretical background. We review specific concerns about the construct validity and translational relevance of individual behavioral tests, outline the limitations of the traditional, symptom-based interpretation, and introduce novel, ethologically relevant frameworks that emphasize simple behavioral patterns. Finally, we explore behavioral monitoring and morphological analysis methods that can be integrated into behavioral testing and discuss how they can enhance the construct validity of these tests.

Rhythmic theta frequency (~5–12 Hz) oscillations coordinate neuronal synchrony and higher frequency oscillations across the cortex. Spatial navigation and context-dependent episodic memories are represented in several interconnected regions including the hippocampal and entorhinal cortices, but the cellular mechanisms for their dynamic coupling remain to be defined. Using monosynaptically-restricted retrograde viral tracing in mice, we identified a subcortical GABAergic input from the medial septum that terminated in the entorhinal cortex, with collaterals innervating the dorsal presubiculum. Extracellularly recording and labeling GABAergic entorhinal-projecting neurons in awake behaving mice show that these subcortical neurons, named orchid cells, fire in long rhythmic bursts during immobility and locomotion. Orchid cells discharge near the peak of hippocampal and entorhinal theta oscillations, couple to entorhinal gamma oscillations, and target subpopulations of extra-hippocampal GABAergic interneurons. Thus, orchid cells are a specialized source of rhythmic subcortical GABAergic modulation of ‘upstream’ and ‘downstream’ cortico-cortical circuits involved in mnemonic functions.

The aim of this study was to determine the seropositivity rate of pharmacists and pharmacy staff after the administration of two doses of the CoronaVac-SinoVac vaccine and to assess changes in their antibody levels according to sociodemographic characteristics. This descriptive study was conducted between June 04, 2021 and September 30, 2021 in pharmacies located in Istanbul, Türkiye. The results of self-initiated immunoglobulin (Ig) G testing of the pharmacists and pharmacy staff, conducted at diagnostic laboratories contracted by the Istanbul Chamber of Pharmacists, were obtained using an online data collection tool. IgG measurements taken from 15 days up to 120 days after the two vaccine doses were included in the study. Participants were asked whether they smoked, had any chronic diseases (hypertension, chronic obstructive pulmonary disease, asthma, diabetes, .), or took any medications. Subgroup analyses were performed for each method used to measure antibody levels. The study included 329 pharmacists/pharmacy staff (298 pharmacists and 31 pharmacy staff). The mean age of the participants was 49.7 ± 13.7 years, and 71.4% were female. The antibody positivity of the 329 participants was 94.9% following the two doses. The positivity rate was 95.4% in participants under 65 years of age, whereas it was 91.8% in those aged 65 years and over. There was no significant difference in the mean age between those with positive and negative antibody results ( > 0.05). Although antibody levels were lower older people, smokers, and those with chronic diseases, this difference was not statistically significant ( > 0.05). Seropositivity developed following the administration of two doses of CoronaVac-Sinovac vaccines. IgG antibody levels were lower in older adults, smokers, and those with chronic diseases, although not to a statistically significant extent. Further studies are needed to better understand the reasons for the different immunological responses to COVID-19.

Medial septal GABAergic neurons of the basal forebrain innervate the hippocampus and related cortical areas, contributing to the coordination of network activity, such as theta oscillations and sharp wave-ripple events, via a preferential innervation of GABAergic interneurons. Individual medial septal neurons display diverse activity patterns, which may be related to their termination in different cortical areas and/or to the different types of innervated interneurons. To test these hypotheses, we extracellularly recorded and juxtacellularly labeled single medial septal neurons in anesthetized rats in vivo during hippocampal theta and ripple oscillations, traced their axons to distant cortical target areas, and analyzed their postsynaptic interneurons. Medial septal GABAergic neurons exhibiting different hippocampal theta phase preferences and/or sharp wave-ripple related activity terminated in restricted hippocampal regions, and selectively targeted a limited number of interneuron types, as established on the basis of molecular markers. We demonstrate the preferential innervation of bistratified cells in CA1 and of basket cells in CA3 by individual axons. One group of septal neurons was suppressed during sharp wave-ripples, maintained their firing rate across theta and non-theta network states and mainly fired along the descending phase of CA1 theta oscillations. In contrast, neurons that were active during sharp wave-ripples increased their firing significantly during “theta” compared to “non-theta” states, with most firing during the ascending phase of theta oscillations. These results demonstrate that specialized septal GABAergic neurons contribute to the coordination of network activity through parallel, target area- and cell type-selective projections to the hippocampus.

RationaleKetamine produces dissociative, psychomimetic, anxiolytic, antidepressant, and anesthetic effects in a dose dependent manner. It has a complex mechanism of action that involve alterations in other glutamate receptors. The metabotropic glutamate receptor 5 (mGluR5) has been investigated in relation to the psychotic and anesthetic properties of ketamine, while its role in mediating the therapeutic effects of ketamine remains unknown.ObjectivesWe investigated the role of mGluR5 on the antidepressant, anxiolytic and fear memory-related effects of ketamine in adult male Wistar rats.MethodsTwo sets of experiments were conducted. We first utilized the positive allosteric modulator CDPPB to investigate how acute mGluR5 activation regulates the therapeutic effects of ketamine (10 mg/kg). We then tested the synergistic antidepressant effect of mGluR5 antagonism and ketamine by combining MTEP with a sub-effective dose of ketamine (1 mg/kg). Behavioral despair, locomotor activity, anxiety-like behavior, and fear memory were respectively assessed in the forced swim test (FST), open field test (OFT), elevated plus maze (EPM), and auditory fear conditioning.ResultsEnhancing mGluR5 activity via CDPPB occluded the antidepressant effect of ketamine without changing locomotor activity. Furthermore, concomitant administration of MTEP and ketamine exhibited a robust synergistic antidepressant effect. The MTEP + ketamine treatment, however, blocked the anxiolytic effect observed by sole administration of MTEP or the low dose ketamine.ConclusionsThese findings suggest that suppressed mGluR5 activity is required for the antidepressant effects of ketamine. Consequently, the antagonism of mGluR5 enhances the antidepressant effectiveness of low dose ketamine, but eliminates its anxiolytic effects.

Humans require social bonds to fulfill their higher-order needs as social beings. The most striking psychological effect of social bonds is the capability of decreasing acute psychological stress--a mental and/or emotional load or tension occurring during negative conditions. This overall positive impact on mood is defined as social buffering. Here, Unal and Kain investigate the behavioral effects of social buffering in rats by evaluating two critical phenomena for survival, namely risk-taking behavior and anxiety.

The perirhinal cortex supports recognition and associative memory. Prior unit recording studies revealed that recognition memory involves a reduced responsiveness of perirhinal cells to familiar stimuli whereas associative memory formation is linked to increasing perirhinal responses to paired stimuli. Both effects are thought to depend on perirhinal plasticity but it is unclear how the same network could support these opposite forms of plasticity. However, a recent study showed that when neocortical inputs are repeatedly activated, depression or potentiation could develop, depending on the extent to which the stimulated neocortical activity recruited intrinsic longitudinal connections. We developed a biophysically realistic perirhinal model that reproduced these phenomena and used it to investigate perirhinal mechanisms of associative memory. These analyzes revealed that associative plasticity is critically dependent on a specific subset of neurons, termed conjunctive cells (CCs). When the model network was trained with spatially distributed but coincident neocortical inputs, CCs acquired excitatory responses to the paired inputs and conveyed them to distributed perirhinal sites via longitudinal projections. CC ablation during recall abolished expression of the associative memory. However, CC ablation during training did not prevent memory formation because new CCs emerged, revealing that competitive synaptic interactions governs the formation of CC assemblies.

Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity. We used retrograde tracing with fluorescent immunohistochemistry to identify cholinergic and non-cholinergic parvalbumin- or calbindin-immunoreactive BF neuronal subgroups targeting the input (lateral and basolateral nuclei) and output (central nucleus and the central bed nucleus of the stria terminalis) regions of the amygdaloid complex. We observed a dense non-cholinergic, putative GABAergic projection from the ventral pallidum (VP) and the substantia innominata (SI) to the basolateral amygdala (BLA). The VP/SI axonal projections to the BLA were confirmed using viral anterograde tracing and transsynaptic labeling. We tested the potential function of this VP/SI-BLA pathway in a 1000-cell biophysically realistic network model, which incorporated principal neurons and three major interneuron groups of the BLA, together with extrinsic glutamatergic, cholinergic, and VP/SI GABAergic inputs. We observed in silico that theta-modulation of VP/SI GABAergic projections enhanced theta oscillations in the BLA via their selective innervation of the parvalbumin-expressing local interneurons. Ablation of parvalbumin-, but not somatostatin- or calretinin-expressing, interneurons reduced theta power in the BLA model. These results suggest that long-range BF GABAergic projections may modulate network activity at their target regions through the formation of a common interneuron-type and oscillatory phase-specific disinhibitory motif.