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Word segmentation is a crucial step in children's vocabulary learning. While computational models of word segmentation can capture infants' performance in small-scale artificial tasks, the examination of early word segmentation in naturalistic settings has been limited by the lack of measures that can relate models' performance to developmental data. Here, we extended CLASSIC (Chunking Lexical and Sublexical Sequences in Children; Jones et al., 2021), a corpus-trained chunking model that can simulate several memory and phonological and vocabulary learning phenomena to allow it to perform word segmentation using utterance boundary information, and we have named this extended version CLASSIC utterance boundary (CLASSIC-UB). Further, we compared our model to the performance of children on a wide range of new measures, capitalizing on the link between word segmentation and vocabulary learning abilities. We showed that the combination of chunking and utterance-boundary information used by CLASSIC utterance boundary allowed a better prediction of English-learning children's output vocabulary than did other models.

Child-directed speech has long been known to influence children's vocabulary learning. However, while we know that caregiver utterances differ from those directed at adults in various ways, little is known about any differences in the lexical properties of child-directed and adult-directed utterances. We compare over half a million word tokens from adult speech directed at children (from caregiver--child transcriptions) to the same quantity directed at adults. We show that child-directed speech contains greater numbers of words that are lower in phonemic length, higher in frequency, lower in phonotactic probability, and higher in neighborhood density than adult-directed speech; furthermore, child-directed speech explains over twice the variability of children's productive noun vocabularies than adult-directed speech. These findings indicate that children's word production is clearly influenced by the characteristics of the words spoken directly to them and that researchers need to be wary of using adult-directed language corpora when calculating lexical measures.

In patch foraging tasks, animals must decide whether to remain with a depleting resource or to leave it in search of a potentially better source of reward. In such tasks, animals consistently follow the general predictions of optimal foraging theory (the marginal value theorem; MVT): to leave a patch when the reward rate in the current patch depletes to the average reward rate across patches. Prior studies implicate an important role for the anterior cingulate cortex (ACC) in foraging decisions based on MVT: within single trials, ACC activity increases immediately preceding foraging decisions, and across trials, these dynamics are modulated as the value of staying in the patch depletes to the average reward rate. Here, we test whether these activity patterns reflect dynamic encoding of decision-variables and whether these signals are directly involved in decision-making. We developed a leaky accumulator model based on the MVT that generates estimates of decision variables within and across trials, and tested model predictions against ACC activity recorded from male rats performing a patch foraging task. Model predicted changes in MVT decision variables closely matched rat ACC activity. Next, we pharmacologically inactivated ACC in male rats to test the contribution of these signals to decision-making. ACC inactivation had a profound effect on rats foraging decisions and response times (RTs) yet rats still followed the MVT decision rule. These findings indicate that the ACC encodes foraging-related variables for reasons unrelated to patch-leaving decisions.SIGNIFICANCE STATEMENT The ability to make adaptive patch-foraging decisions, to remain with a depleting resource or search for better alternatives, is critical to animal well-being. Previous studies have found that anterior cingulate cortex (ACC) activity is modulated at different points in the foraging decision process, raising questions about whether the ACC guides ongoing decisions or serves a more general purpose of regulating cognitive control. To investigate the function of the ACC in foraging, the present study developed a dynamic model of behavior and neural activity, and tested model predictions using recordings and inactivation of ACC. Findings revealed that ACC continuously signals decision variables but that these signals are more likely used to monitor and regulate ongoing processes than to guide foraging decisions.

Recent evidence indicates that children represent and learn multiple meanings of ambiguous words from early in development (e.g., mail letter, alphabetic letter). This raises the question of which naturalistic factors might allow young children to resolve lexical ambiguities. Previous research has shown that children’s processing of ambiguous words is facilitated by verb-related information. However, it is still unclear whether such facilitation comes from bottom-up (lexical associations) or top-down information sources (verb-event structures). In this study, we leveraged a large sense-annotated child-directed speech corpus to disentangle the effect of bottom-up lexical and top-down event structure cues. Preliminary results show that 4-year-olds might rely on verb-event structures when these are put in competition with lexical association. We discuss implications for theories of sentence parsing and word learning.

Frequency counters are computational mechanisms that track the frequency or probability of speech units. Such counters are idealizations which re-describe frequency effects in early word segmentation, not providing an underlying learning mechanism from which these effects arise. Previous work has shown that Implicit Chunking represents a plausible learning mechanism explaining infants’ sensitivity to statistical cues when segmenting small-scale artificial languages (French et al., 2011). However, no work has examined whether Implicit Chunking allows to segment naturalistic speech in a developmentally plausible way. Here, we show how a novel symbolic model of Implicit Chunking – CLASSIC-Utterance-Boundary - performs better or as well as previous frequency-based models (i.e., transitional probability, chunking) at predicting children’s word age of first production and a range of word-level characteristics of children’s vocabularies (word frequency, word length, neighborhood density, phonotactic probability). We suggest that explicit frequency counters are not necessary to explain infants’ speech segmentation in naturalistic settings.

The locus coeruleus (LC), or blue spot, is a small nucleus located deep in the brainstem that provides the far-reaching noradrenergic neurotransmitter system of the brain. This phylogenetically conserved nucleus has proved relatively intractable to full characterization, despite more than 60 years of concerted efforts by investigators. Recently, an array of powerful new neuroscience tools have provided unprecedented access to this elusive nucleus, revealing new levels of organization and function. We are currently at the threshold of major discoveries regarding how this tiny brainstem structure exerts such varied and significant influences over brain function and behaviour. All LC neurons receive inputs related to autonomic arousal, but distinct subpopulations of those neurons can encode specific cognitive processes, presumably through more specific inputs from the forebrain areas. This ability, combined with specific patterns of innervation of target areas and heterogeneity in receptor distributions, suggests that activation of the LC has more specific influences on target networks than had initially been imagined.

Concurrent learning of adjacent and nonadjacent dependencies has been shown in adults only. This study extended this line of research by examining dependency-specific learning for both adjacent and nonadjacent dependencies concurrently in both adults and children. Seventy adults aged 18 to 64 (40 women, 30 men; Experiment 1) and 64 children aged 10 to 11 years (40 girls, 24 boys; Experiment 2) were tested with a new serial reaction time (SRT) task in which they were trained for 5-8 min on materials comprising equally probable adjacent and nonadjacent dependencies. They were then asked to discriminate between trained and untrained dependencies in a familiarity task. Both adults and children showed implicit concurrent learning of both adjacent and nonadjacent dependencies. The two dependency types were learned to the same extent. However, adults showed a rapid, sustainable, and dependency-specific sensitivity throughout the SRT task while children only showed a dependency-specific sensitivity to violations of expectations after exposure. When the two groups were statistically compared, only adults showed a dependency-specific learning effect after exposure. These findings are in line with the age-related improvement model of dependency learning.

Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles in addiction-related behaviors are still debated. Here, we targeted VTA DA neurons for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, and relapse-related behaviors in male rats, querying the roles of DA neuron inhibitory and excitatory G-protein signaling in these processes. Designer receptor stimulation of Gq signaling, but not Gs signaling, in DA neurons enhanced cocaine seeking via functionally distinct projections to forebrain limbic regions. In contrast, engaging inhibitory Gi/o signaling in DA neurons blunted the reinforcing and priming effects of cocaine, reduced stress-potentiated reinstatement, and altered behavioral strategies for cocaine seeking and taking. Results demonstrate that DA neurons play several distinct roles in cocaine seeking, depending on behavioral context, G-protein-signaling cascades, and DA neuron efferent targets, highlighting their multifaceted roles in addiction.SIGNIFICANCE STATEMENT G-protein-coupled receptors are crucial modulators of ventral tegmental area (VTA) dopamine neuron activity, but how this metabotropic signaling impacts the complex roles of dopamine in reward and addiction is poorly understood. Here, we bidirectionally modulate dopamine neuron G-protein signaling with DREADDs (designer receptors exclusively activated by designer drugs) during a variety of cocaine-seeking behaviors, revealing nuanced, pathway-specific roles in cocaine reward, effortful seeking, and relapse-like behaviors. Gq and Gs stimulation activated dopamine neurons, but only Gq stimulation robustly enhanced cocaine seeking. Gi/o inhibitory signaling reduced some, but not all, types of cocaine seeking. Results show that VTA dopamine neurons modulate numerous distinct aspects of cocaine addiction- and relapse-related behaviors, and point to potential new approaches for intervening in these processes to treat addiction.

Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories.

BackgroundDrug cues recruit prelimbic cortex neurons that project to ipsilateral nucleus accumbens core. However, it is not known if the same is true for prelimbic cortex projections that decussate to innervate contralateral nucleus accumbens core. Further, a role for prelimbic cortex dopamine signaling in cued reinstatement of cocaine seeking has not been shown.MethodsWe assessed Fos expression in prelimbic cortex neurons that project to contralateral nucleus accumbens core following cued reinstatement of cocaine or sucrose seeking. We also tested the effect of intra-prelimbic cortex infusions of the D1/D2 antagonist fluphenazine on cued cocaine and sucrose seeking.ResultsPrelimbic cortex-contralateral nucleus accumbens core projections were activated by cocaine cues but not sucrose cues, and this activation correlated with reinstatement behavior. Blockade of prelimbic cortex dopamine signaling prevented cued reinstatement of cocaine- but not sucrose-seeking behavior.ConclusionsCued cocaine seeking is associated with activation of the prelimbic cortex-contralateral nucleus accumbens core pathway. Prelimbic cortex dopamine signaling is necessary for cues to reinstate drug-seeking behavior.

Spike frequency adaptation (SFA or accommodation) and calcium-activated potassium channels that underlie after-hyperpolarization potentials (AHP) regulate repetitive firing of neurons. Precisely how neuromodulators such as dopamine from the ventral tegmental area (VTA) regulate SFA and AHP (together referred to as intrinsic inhibition) in the prefrontal cortex (PFC) remains unclear. Using whole cell electrophysiology, we measured intrinsic inhibition in prelimbic (PL) layer 5 pyramidal cells of male adult rats. Results demonstrate that bath application of dopamine reduced intrinsic inhibition (EC50: 25.0 μmol/L). This dopamine action was facilitated by coapplication of cocaine (1 μmol/L), a blocker of dopamine reuptake. To evaluate VTA dopamine terminals in PFC slices, we transfected VTA dopamine cells of TH::Cre rats in vivo with Cre-dependent AAVs to express channelrhodopsin-2 (ChR2) or designer receptors exclusively activated by designer drugs (DREADDS). In PFC slices from these animals, stimulation of VTA terminals with either blue light to activate ChR2 or bath application of clozapine-N-oxide (CNO) to activate Gq-DREADDs produced a similar reduction in intrinsic inhibition in PL neurons. Electrophysiological recordings from cells expressing retrograde fluorescent tracers showed that this plasticity occurs in PL neurons projecting to the accumbens core. Collectively, these data highlight an ability of VTA terminals to gate intrinsic inhibition in the PFC, and under appropriate circumstances, enhance PL neuronal firing. These cellular actions of dopamine may be important for dopamine-dependent behaviors involving cocaine and cue-reward associations within cortical-striatal circuits.

Statistical learning paradigms traditionally use transitionalprobabilities as a measure of statistical distribution within alanguage. The current study suggests that alternative metricsmay exist that can account for differences in languageprocessing ability. Two primed lexical decision tasks are usedto examine the effects of bigram frequency and diversity onspeed and accuracy of word recognition. It is demonstratedthat both frequency and diversity contribute to wordrecognition performance; findings and theoreticalimplications are discussed.

One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction. We describe evidence collected over the past 10 years that elaborates the role of orexin in drug seeking under circumstances where high levels of effort are required to obtain the drug, or when motivation for drug reward is augmented by the presence of external stimuli like drug-associated cues/contexts or stressors. Evidence from studies using traditional self-administration and reinstatement models, as well as behavioral economic analyses of drug demand elasticity, clearly delineates a role for orexin in modulating motivational, rather than the primary reinforcing aspects of drug reward. We also discuss the anatomical interconnectedness of the orexin system with wider motivation and reward circuits, with a particular focus on how orexin modulates prefrontal and other glutamatergic inputs onto ventral tegmental area dopamine neurons. Last, we look ahead to the next decade of the research in this area, highlighting the recent FDA approval of the dual orexin receptor antagonist suvorexant (Belsomra®) for the treatment of insomnia as a promising sign of the potential clinical utility of orexin-based therapies for the treatment of addiction.

Despite numerous efforts to align educational practice more closely with findings from educational research, there is little clarity about how educational practitioners can, in principle, use research. We propose a conceptualisation based on how research can contribute to practitioners' thinking: specifically, our framework proposes that research can inform bounded decision-making, teachers' reflection and organisational learning. Practitioners can also use research without being aware that they are doing so. We argue that this conceptualisation of research use has potential to inform researchers and practitioners.

Our understanding of human brain function can be greatly aided by studying analogous brain structures in other organisms. One brain structure with neurochemical and anatomical homology throughout vertebrate species is the locus coeruleus (LC), a small collection of norepinephrine (NE)-containing neurons in the brainstem that project throughout the central nervous system. The LC is involved in nearly every aspect of brain function, including arousal and learning, which has been extensively examined in rats and nonhuman primates using single-unit recordings. Recent work has expanded into putative LC single-unit electrophysiological recordings in a nonmodel species, the zebra finch. Given the importance of correctly identifying analogous structures as research efforts expand to other vertebrates, we suggest adoption of consensus anatomical and electrophysiological guidelines for identifying LC neurons across species when evaluating brainstem single-unit spiking or calcium imaging. Such consensus criteria will allow for confident cross-species understanding of the roles of the LC in brain function and behavior. [ABSTRACT FROM AUTHOR]

UnlabelledGlutamate inputs to nucleus accumbens (NAc) facilitate conditioned drug-seeking behavior and primarily originate from medial prefrontal cortex (mPFC), basolateral amygdala (BLA), and ventral subiculum of the hippocampus (vSub). These regions express Fos (a marker of neural activity) during cue-induced reinstatement of cocaine seeking, but only subpopulations of neurons within these regions drive drug seeking. One way to identify and functionally distinguish neural subpopulations activated during drug-seeking is to examine their projection targets. In rats, we examined Fos expression during cue-induced reinstatement of cocaine- and sucrose-seeking in prelimbic cortex (PL), infralimbic cortex (IL), BLA, and vSub neurons that project to NAc core (NAcC) or NAc shell (NAcSh). Neurons in PL, BLA, and vSub that project to NAcC, but not NAcSh, expressed Fos during cue-induced cocaine seeking, but not sucrose seeking. However, only activation of the PL-NAcC pathway positively correlated with cocaine reinstatement behavior, unlike BLA or vSub inputs to NAcC. To confirm a functional role for the PL-NAcC pathway, and to test the hypothesis that this pathway is recruited in a dopamine-dependent manner, we used a pharmacological disconnection approach whereby dopamine signaling was blocked in PL and glutamate signaling was blocked in the contralateral NAcC. This disconnection attenuated cue-induced reinstatement of cocaine seeking but had no effect on reinstatement of sucrose seeking. Our results highlight a role for the PL-NAcC pathway in cocaine seeking and show that these glutamatergic projections are recruited in a dopamine-dependent manner to drive reinstatement.Significance statementRelapse represents a significant barrier to the successful treatment of cocaine addiction. Here, we characterize the relative activation of glutamatergic inputs to nucleus accumbens during cued reinstatement of cocaine seeking versus sucrose seeking. Prelimbic cortex (PL) projections to nucleus accumbens core (NAcC) uniquely expressed Fos in a manner that positively correlated with cocaine-seeking, but not sucrose-seeking, behavior. Additional functional experiments showed that the PL-NAcC pathway was recruited by drug-associated cues in a dopamine-dependent manner to drive cocaine-seeking, but not sucrose-seeking, behavior. These data highlight PL neurons that project to NAcC, and their regulation by dopamine, as potential targets for therapeutics designed to treat cocaine relapse that do not affect natural reward seeking.

In this paper we examine how a mechanism that learns wordclasses from distributional information can contribute to thesimulation of child language. Using a novel measure of nounrichness, it is shown that the ratio of nouns to verbs in youngchildren’s speech is considerably higher than in adult speech.Simulations with MOSAIC show that this effect can bepartially (but not completely) explained by an utterance-finalbias in learning. The remainder of the effect is explained bythe early emergence of a productive noun category, which canbe learned through distributional analysis.

In this paper we evaluate a mechanism for the learning of wordcategories from distributional information against criteria ofpsychological plausibility. We elaborate on the ideasdeveloped by Redington et al. (1998) by embedding themechanism in an existing model of language acquisition(MOSAIC) and gradually expanding the contexts it has accessto in a developmentally plausible way. In line with child data,the mechanism shows early development of a noun category,and later development of a verb category. It is furthermoreshown that the mechanism can maintain high performance atlower computational overhead by disregarding tokenfrequency information, thus improving the plausibility of themechanism as something that is used by language-learningchildren.

One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction. We describe evidence collected over the past 10 years that elaborates the role of orexin in drug seeking under circumstances where high levels of effort are required to obtain the drug, or when motivation for drug reward is augmented by the presence of external stimuli like drug-associated cues/contexts or stressors. Evidence from studies using traditional self-administration and reinstatement models, as well as behavioral economic analyses of drug demand elasticity, clearly delineates a role for orexin in modulating motivational, rather than the primary reinforcing aspects of drug reward. We also discuss the anatomical interconnectedness of the orexin system with wider motivation and reward circuits, with a particular focus on how orexin modulates prefrontal and other glutamatergic inputs onto ventral tegmental area dopamine neurons. Last, we look ahead to the next decade of the research in this area, highlighting the recent FDA approval of the dual orexin receptor antagonist suvorexant (Belsomra®) for the treatment of insomnia as a promising sign of the potential clinical utility of orexin-based therapies for the treatment of addiction.

This paper describes an extension to the MOSAIC modelwhich aims to increase MOSAIC’s fit to the cross-linguisticoccurrence of Optional Infinitive (OI) errors. While previousversions of MOSAIC have successfully simulated these errorsas truncated compound finites with missing modals orauxiliaries, they have tended to underestimate the rate of OIerrors in (some) obligatory subject languages. Here, weexplore defaulting effects, where the most frequent form of agiven verb is substituted for less frequent forms, as anadditional source of OI errors. It is shown that defaulting inEnglish tends to result in the production of bare forms that areindistinguishable from the infinitive, while defaulting inSpanish is less pronounced, and tends to result in theproduction of 3rd person singular forms. Dutch verb forms aredominated by the stem in corpus-wide statistics, and theinfinitive in utterance-final position, suggesting defaulting inDutch may change qualitatively across development.Defaulting is shown to increase MOSAIC’s fit to English andDutch without affecting its already good fit to Spanish, andprovides a potential way of simulating the cross-linguisticpattern of verb-marking errors in children with SLI.

Orexins (hypocretins) are two peptides (orexin A and B) produced from the pre-pro-orexin precursor and expressed in a limited region of dorsolateral hypothalamus. Orexins were originally thought to specifically mediate feeding and promote wakefulness, but it is now clear that they participate in a wide range of behavioral and physiological processes under select circumstances. Orexins primarily mediate behavior under situations of high motivational relevance, such as during physiological need states, exposure to threats or reward opportunities. We hypothesize that many behavioral functions of orexins (including regulation of sleep/wake cycling) reflect a fundamentally integrated function for orexins in translating motivational activation into organized suites of psychological and physiological processes supporting adaptive behaviors. We also discuss how numerous forms of neural heterogeneity modulate this function, allowing orexin neurons to organize diverse, adaptive responses in a variety of motivationally relevant situations. Thus, the involvement of orexins in diverse behaviors may reflect a common underlying function for this peptide system.

The ventral pallidum is centrally positioned within mesocorticolimbic reward circuits, and its dense projection to the ventral tegmental area (VTA) regulates neuronal activity there. However, the ventral pallidum is a heterogeneous structure, and how this complexity affects its role within wider reward circuits is unclear. We found that projections to VTA from the rostral ventral pallidum (RVP), but not the caudal ventral pallidum (CVP), were robustly Fos activated during cue-induced reinstatement of cocaine seeking--a rat model of relapse in addiction. Moreover, designer receptor-mediated transient inactivation of RVP neurons, their terminals in VTA or functional connectivity between RVP and VTA dopamine neurons blocked the ability of drug-associated cues (but not a cocaine prime) to reinstate cocaine seeking. In contrast, CVP neuronal inhibition blocked cocaine-primed, but not cue-induced, reinstatement. This double dissociation in ventral pallidum subregional roles in drug seeking is likely to be important for understanding the mesocorticolimbic circuits underlying reward seeking and addiction.

The initiation of abstinence after chronic drug self-administration is stressful. Cocaine-seeking behavior on the first day of the absence of the expected drug (Extinction Day 1, ED1) is reduced by blocking 5-HT signaling in dorsal hippocampal cornu ammonis 1 (CA1) in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior and that dorsal raphe (DR) serotonin (5-HT) input to CA1 may be involved. We inhibited 5-HT1A/1B receptors (WAY-100635 plus GR-127935), or DR input (chemogenetics), in CA1 on ED1 to test the role of this pathway on cocaine-seeking persistence 2 weeks later. We also inhibited 5-HT1A or 5-HT1B receptors in CA1 during conditioned place preference (CPP) for cocaine, to examine mechanisms involved in the persistent effects of ED1 manipulations. Inhibition of DR inputs, or 5-HT1A/1B signaling, in CA1 decreased drug seeking on ED1 and decreased cocaine seeking 2 weeks later revealing that 5-HT signaling in CA1 during ED1 contributes to persistent drug seeking during abstinence. In addition, 5-HT1B antagonism alone transiently decreased drug-associated memory performance when given prior to a CPP test, whereas similar antagonism of 5-HT1A alone had no such effect but blocked CPP retrieval on a test 24 h later. These CPP findings are consistent with prior work showing that DR inputs to CA1 augment recall of the drug-associated context and drug seeking via 5-HT1B receptors and prevent consolidation of the updated nondrug context via 5-HT1A receptors. Thus, treatments that modulate 5-HT--dependent memory mechanisms in CA1 during initial abstinence may facilitate later maintenance of abstinence. [ABSTRACT FROM AUTHOR]