The frequency of human social and emotional disorders varies significantly between males and females. We have recently reported that oxytocin receptor interneurons (OxtrINs) modulate female ...sociosexual behavior. Here, we show that, in male mice, OxtrINs regulate anxiety-related behaviors. We demonstrate that corticotropin-releasing-hormone-binding protein (CRHBP), an antagonist of the stress hormone CRH, is specifically expressed in OxtrINs. Production of CRHBP blocks the CRH-induced potentiation of postsynaptic layer 2/3 pyramidal cell activity of male, but not female, mice, thus producing an anxiolytic effect. Our data identify OxtrINs as critical for modulation of social and emotional behaviors in both females and males and reveal a molecular mechanism that acts on local medial prefrontal cortex (mPFC) circuits to coordinate responses to OXT and CRH. They suggest that additional studies of the impact of the OXT/OXTR and CRHBP/CRH pathways in males and females will be important in development of gender-specific therapies.
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•Activation of OxtrINs is anxiolytic in males and prosocial in females•OxtrINs specifically express CRHBP, an inhibitor of the stress hormone CRH•CRHBP blocks activation of layer 2/3 pyramidal cells by CRH only in males•OxtrINs in the mPFC coordinate sexually dimorphic social/emotional behaviors
A population of oxytocin-responsive neurons blocks anxiety-related behaviors in male, but not female, mice, suggesting a basis for sex-specific differences observed in some emotional disorders.
Invasive alien species (IAS) threaten human livelihoods and biodiversity globally. Increasing globalization facilitates IAS arrival, and environmental changes, including climate change, facilitate ...IAS establishment. Here we provide the first global, spatial analysis of the terrestrial threat from IAS in light of twenty-first century globalization and environmental change, and evaluate national capacities to prevent and manage species invasions. We find that one-sixth of the global land surface is highly vulnerable to invasion, including substantial areas in developing economies and biodiversity hotspots. The dominant invasion vectors differ between high-income countries (imports, particularly of plants and pets) and low-income countries (air travel). Uniting data on the causes of introduction and establishment can improve early-warning and eradication schemes. Most countries have limited capacity to act against invasions. In particular, we reveal a clear need for proactive invasion strategies in areas with high poverty levels, high biodiversity and low historical levels of invasion.
Behavioral flexibility and impulse control are necessary for successful execution of adaptive behavior. They are impaired in patients with damage to the prefrontal cortex (PFC) and in some clinically ...important conditions, such as obsessive-compulsive disorder. Although the medial prefrontal cortex (mPFC) has been investigated as a critical structure for behavioral flexibility and impulse control, the contribution of the underlying pyramidal neuron cell types in the mPFC remained to be understood. Here we show that interneuron-mediated local inactivation of pyramidal neurons in the mPFC of male and female mice induces both premature responses and choice bias, and establish that these impulsive and compulsive responses are modulated independently. Cell-type-specific photoinhibition of pyramidal deep layer corticostriatal or corticothalamic neurons reduces behavioral flexibility without inducing premature responses. Together, our data confirm the role of corticostriatal neurons in behavioral flexibility and demonstrate that flexible behaviors are also modulated by direct projections from deep layer corticothalamic neurons in the mPFC to midline thalamic nuclei.
Behavioral flexibility and impulse control are indispensable for animals to adapt to changes in the environment and often affected in patients with PFC damage and obsessive-compulsive disorder. We used a probabilistic reversal task to dissect the underlying neural circuitry in the mPFC. Through characterization of the three major pyramidal cell types in the mPFC with optogenetic silencing, we demonstrated that corticostriatal and corticothalamic but not corticocortical pyramidal neurons are temporally recruited for behavioral flexibility. Together, our findings confirm the role of corticostriatal projections in cognitive flexibility and identify corticothalamic neurons as equally important for behavioral flexibility.
Neuromodulatory substances can be released from distal afferents for communication between brain structures or produced locally to modulate neighboring circuit elements. Corticotropin-releasing ...hormone (CRH) from long-range neurons in the hypothalamus projecting to the medial prefrontal cortex (mPFC) has been shown to induce anxiety-like behaviors. However, the role of CRH produced in the mPFC has not been investigated. Here we demonstrate that a specific class of mPFC interneurons that express CRH (CrhINs) releases CRH upon high-frequency stimulation to enhance excitability of layer 2/3 pyramidal cells (L2/3 PCs) expressing the CRH receptors. When stimulated at low frequency, CrhINs release GABA resulting in the inhibition of oxytocin receptor-expressing interneurons (OxtrINs) and L2/3 PCs. Conditional deletion of CRH in mPFC CrhINs and chemogenetic activation of CrhINs have opposite effects on novelty exploration in male but not in female mice, and do not affect anxiety-related behaviors in either males or females. Our data reveal that CRH produced by local interneurons in the mPFC is required for sex-specific novelty exploration and suggest that our understanding of complex behaviors may require knowledge of local and remote neuromodulatory action.
A great deal of interest has been focused recently on the habenula and its critical role in aversion, negative-reward and drug dependence. Using a conditional mouse model of the ACh-synthesizing ...enzyme choline acetyltransferase (Chat), we report that local elimination of acetylcholine (ACh) in medial habenula (MHb) neurons alters glutamate corelease and presynaptic facilitation. Electron microscopy and immuno-isolation analyses revealed colocalization of ACh and glutamate vesicular transporters in synaptic vesicles (SVs) in the central IPN. Glutamate reuptake in SVs prepared from the IPN was increased by ACh, indicating vesicular synergy. Mice lacking CHAT in habenular neurons were insensitive to nicotine-conditioned reward and withdrawal. These data demonstrate that ACh controls the quantal size and release frequency of glutamate at habenular synapses, and suggest that the synergistic functions of ACh and glutamate may be generally important for modulation of cholinergic circuit function and behavior.
A large number of studies have demonstrated that the nucleus accumbens (NAC) is a critical site in the neuronal circuits controlling reward responses, motivation, and mood, but the neuronal cell ...type(s) underlying these processes are not yet known. Identification of the neuronal cell types that regulate depression-like states will guide us in understanding the biological basis of mood and its regulation by diseases like major depressive disorder. Taking advantage of recent findings demonstrating that the serotonin receptor chaperone, p11, is an important molecular regulator of depression-like states, here we identify cholinergic interneurons (CINs) as a primary site of action for p11 in the NAC. Depression-like behavior is observed in mice after decrease of p11 levels in NAC CINs. This phenotype is recapitulated by silencing neuronal transmission in these cells, demonstrating that accumbal cholinergic neuronal activity regulates depression-like behaviors and suggesting that accumbal CIN activity is crucial for the regulation of mood and motivation.
Objective
A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies inflammation and joint deformation. Patients with RA rate pain relief as the highest priority; however, few ...studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways. The ω‐conotoxin MVIIA (ziconotide) is used in humans to alleviate persistent pain syndromes, because it specifically blocks the voltage‐gated calcium 2.2 (CaV2.2) channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The aims of this study were to investigate whether blockade of CaV2.2 can suppress arthritis pain, and to examine the progression of induced arthritis during persistent CaV2.2 blockade.
Methods
Transgenic mice expressing a membrane‐tethered form of MVIIA under the control of a nociceptor‐specific gene (MVIIA‐transgenic mice) were used in the experiments. The mice were subjected to unilateral induction of joint inflammation using a combination of antigen and collagen.
Results
CaV2.2 blockade mediated by tethered MVIIA effectively suppressed arthritis‐induced pain; however, in contrast to their wild‐type littermates, which ultimately regained use of their injured joint as inflammation subsided, MVIIA‐transgenic mice showed continued inflammation, with up‐regulation of the osteoclast activator RANKL and concomitant joint and bone destruction.
Conclusion
Taken together, our results indicate that alleviation of peripheral pain by blockade of CaV2.2‐ mediated calcium influx and signaling in nociceptor sensory neurons impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV2.2 channel blockers as analgesics during inflammation.
Over the last decade, the understanding of the habenula has rapidly advanced from being an understudied brain area with the Latin name ‘habena” meaning “little rein”, to being considered a “major ...rein” in the control of key monoaminergic brain centers. This ancient brain structure is a strategic node in the information flow from fronto-limbic brain areas to brainstem nuclei. As such, it plays a crucial role in regulating emotional, motivational, and cognitive behaviors and has been implicated in several neuropsychiatric disorders, including depression and addiction. This review will summarize recent findings on the medial (MHb) and lateral (LHb) habenula, their topographical projections, cell types, and functions. Additionally, we will discuss contemporary efforts that have uncovered novel molecular pathways and synaptic mechanisms with a focus on MHb-Interpeduncular nucleus (IPN) synapses. Finally, we will explore the potential interplay between the habenula's cholinergic and non-cholinergic components in coordinating related emotional and motivational behaviors, raising the possibility that these two pathways work together to provide balanced roles in reward prediction and aversion, rather than functioning independently.
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Abstract
The encroachment of invasive shrubs in forest understories can have detrimental effects on native plant recruitment. As a result, removal of invasive species is a common practice although ...long‐lasting success is rare. In order to effectively conserve and manage invaded forests, it is crucial to understand the mechanisms that drive shrub invasion, that is, high propagule pressure, low native resistance and exploitation of empty niches.
To gain a deeper understanding of the invasion process in forest ecosystems we conducted a meta‐analysis of the work done in this topic. We collected data on invasive species and native community performance, and on the abiotic conditions of forest understories under low and high levels of shrub invasion. We analysed data from 124 articles that yielded 377 unique observations.
Our results revealed that while invader performance did not vary by the mechanism of invasion, the impact on the native community was significantly detrimental when invasion occurred via low biotic resistance, and only marginally significant via propagule pressure. Invasive species performance was associated with increases in light availability, but not with other resources (soil water or nutrients). When assessing impact on native performance as a function of invasive performance, results were again only significant under the low biotic resistance mechanism. Lastly, impacts were stronger when invasion took place by a single invader.
Synthesis and applications
. Taken together, these results suggest that restoration efforts should focus on (i) increasing the presence of strong native competitors or functionally diverse native communities, (ii) decreasing sources of invasive shrub propagules while keeping the canopies closed when invasion occurs via high propagule pressure, (iii) avoiding management techniques that degrade or diminish canopy cover and (iv) prioritizing management of forest understories dominated by particularly impactful invasive shrubs.
Resumo
A ocupação de sub‐bosques florestais por arbustos invasores pode ter efeitos negativos no recrutamento de plantas nativas. Consequentemente, a remoção de espécies invasoras é uma prática comum, embora o sucesso a longo prazo seja raro. Para que a conservação e o manejo de florestas invadidas sejam efetivos, é fundamental compreender os mecanismos que levam à invasão por arbustos invasores, ou seja, alta pressão de propágulos, baixa resistência biótica das espécies nativas, e a exploração de nichos vazios.
Para aprofundar o conhecimento sobre o processo de invasão de ecossistemas florestais, nós conduzimos uma meta‐análise dos trabalhos publicados neste tópico. Nós coletamos dados sobre o desempenho de espécies de plantas invasoras e communidades de nativas, além das condições abióticas de sub‐bosques florestais sob níveis baixos e altos de invasão por arbutos não‐nativos. Nós analisamos dados de 124 artigos que resultaram em 377 observações únicas.
Nossos resultados revelaram que, enquanto o desempenho de arbustos invasores não variou de acordo com o mecanismo de invasão, o impacto na comunidade nativa foi significativamente mais prejudicial quando a invasão ocorreu em decorrência da baixa resistência biótica das espécies nativas, e marginalmente significativo quando associada à pressão por propágulos de arbustos invasores. O desempenho de espécies invasoras esteve associado a aumentos de disponibilidade de luz, mas não à disponibilidade de outros recursos (água ou nutrientes do solo). Ao avaliar o impacto no desempenho da comunidade nativa em relação ao desempenho das espécies invasoras, novamente, os resultados foram somente siginificativos se o mecanismo de invasão foi relacionado com a baixa resistência biótica das espécies nativas. Por fim, os impactos foram mais intensos quando a invasão ocurreu por apenas uma espécie invasora.
Síntese e aplicações
. Coletivamente, esses resultados sugerem que esforços de restauração devem focar em (i) aumentar a presença de espécies nativas que são fortes competidoras ou comunidades nativas functionalmente diversas, (ii) diminuir as fontes de propágulos de espécies invasoras e, ao mesmo tempo, manter os dosséis florestais fechados quando a invasão ocorre em decorrência da alta pressão de propágulos, (iii) evitar o uso de técnicas de manejo que degradem ou dimnuam a cobertura do dossel florestal, e (iv) priorizar o manejo de sub‐bosques florestais dominados por uma espécie de arbusto invasor que seja particularmente impactante.
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