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Kfir, N, Lev-Maor G, Glaich O, Alajem A, Datta A, Sze SK, Meshorer E, Ast G.  2015.  SF3B1 Association with Chromatin Determines Splicing Outcomes.. Cell reports. Abstract
Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. One probable explanation lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicate that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses reveal that SF3B1 specifically binds nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affects splicing of these exons similarly to SF3B1 knockdown. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice-site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure.
Travis, KE, Golden NH, Feldman HM, Solomon M, Nguyen J, Mezer A, Yeatman JD, Dougherty RF.  2015.  Abnormal white matter properties in adolescent girls with anorexia nervosa.. NeuroImage. Clinical. 9:648-59. Abstract
Anorexia nervosa (AN) is a serious eating disorder that typically emerges during adolescence and occurs most frequently in females. To date, very few studies have investigated the possible impact of AN on white matter tissue properties during adolescence, when white matter is still developing. The present study evaluated white matter tissue properties in adolescent girls with AN using diffusion MRI with tractography and T1 relaxometry to measure R1 (1/T1), an index of myelin content. Fifteen adolescent girls with AN (mean age = 16.6 years ± 1.4) were compared to fifteen age-matched girls with normal weight and eating behaviors (mean age = 17.1 years ± 1.3). We identified and segmented 9 bilateral cerebral tracts (18) and 8 callosal fiber tracts in each participant's brain (26 total). Tract profiles were generated by computing measures for fractional anisotropy (FA) and R1 along the trajectory of each tract. Compared to controls, FA in the AN group was significantly decreased in 4 of 26 white matter tracts and significantly increased in 2 of 26 white matter tracts. R1 was significantly decreased in the AN group compared to controls in 11 of 26 white matter tracts. Reduced FA in combination with reduced R1 suggests that the observed white matter differences in AN are likely due to reductions in myelin content. For the majority of tracts, group differences in FA and R1 did not occur within the same tract. The present findings have important implications for understanding the neurobiological factors underlying white matter changes associated with AN and invite further investigations examining associations between white matter properties and specific physiological, cognitive, social, or emotional functions affected in AN.
Barbash, S.  2015.  Dynamics of social network structure for Alzheimer and Lymphoma scientific communities.. Biology direct. 10(1):6. Abstract
It is generally assumed that sociology affects scientific progress but specific examples of this assumption are hard to find. We examined this hypothesis by comparing the social network structure and its dynamics over the last 16 years, for two common human diseases; Alzheimer's disease, for which there has been very little therapeutic progress, and Lymphoma, were there has been significant therapeutic progress. We found that the Alzheimer's research community is more interlinked ('dense') and more 'cliquish' than that of Lymphoma and suggest that this could affect its scientific progress.
Kalcheim, C.  2015.  Epithelial-Mesenchymal Transitions during Neural Crest and Somite Development.. Journal of clinical medicine. 5(1) Abstract
Epithelial-to-mesenchymal transition (EMT) is a central process during embryonic development that affects selected progenitor cells of all three germ layers. In addition to driving the onset of cellular migrations and subsequent tissue morphogenesis, the dynamic conversions of epithelium into mesenchyme and vice-versa are intimately associated with the segregation of homogeneous precursors into distinct fates. The neural crest and somites, progenitors of the peripheral nervous system and of skeletal tissues, respectively, beautifully illustrate the significance of EMT to the above processes. Ongoing studies progressively elucidate the gene networks underlying EMT in each system, highlighting the similarities and differences between them. Knowledge of the mechanistic logic of this normal ontogenetic process should provide important insights to the understanding of pathological conditions such as cancer metastasis, which shares some common molecular themes.
Rokem, A, Yeatman JD, Pestilli F, Kay KN, Mezer A, van der Walt S, Wandell BA.  2015.  Evaluating the accuracy of diffusion MRI models in white matter.. PloS one. 10(4):e0123272. Abstract
Models of diffusion MRI within a voxel are useful for making inferences about the properties of the tissue and inferring fiber orientation distribution used by tractography algorithms. A useful model must fit the data accurately. However, evaluations of model-accuracy of commonly used models have not been published before. Here, we evaluate model-accuracy of the two main classes of diffusion MRI models. The diffusion tensor model (DTM) summarizes diffusion as a 3-dimensional Gaussian distribution. Sparse fascicle models (SFM) summarize the signal as a sum of signals originating from a collection of fascicles oriented in different directions. We use cross-validation to assess model-accuracy at different gradient amplitudes (b-values) throughout the white matter. Specifically, we fit each model to all the white matter voxels in one data set and then use the model to predict a second, independent data set. This is the first evaluation of model-accuracy of these models. In most of the white matter the DTM predicts the data more accurately than test-retest reliability; SFM model-accuracy is higher than test-retest reliability and also higher than the DTM model-accuracy, particularly for measurements with (a) a b-value above 1000 in locations containing fiber crossings, and (b) in the regions of the brain surrounding the optic radiations. The SFM also has better parameter-validity: it more accurately estimates the fiber orientation distribution function (fODF) in each voxel, which is useful for fiber tracking.
Hochstein, S, Pavlovskaya M, Bonneh YS, Soroker N.  2015.  Global statistics are not neglected.. Journal of vision. 15(4):7. Abstract
In the framework of Reverse Hierarchy Theory it was suggested that initial vision at a glance brings the gist of the scene to conscious perception using explicit high cortical level representations, which are initially built by implicit bottom-up processing (Hochstein & Ahissar, 2002). Only later return to lower cortical level representations introduces local details to conscious perception. Global statistics of similar elements are perceived rapidly and accurately, suggesting they are included in the initial perception of the gist of the scene, not depending on prior conscious perception of local details. Patients with unilateral spatial neglect have difficulty responding to elements in their contralesional hemifield. However, this deficit is especially pronounced for tasks that require focused attention, i.e., are dependent on the reverse-hierarchy return. We review recent studies that indicate that perception of global statistics is among the spread attention tasks that are somewhat spared from this deficit. Combining these results, we suggest that perhaps the function of global statistics perception might include serving as a basic percept required for finding salient deviants from the mean, as in rapid odd element feature search paradigms, and perhaps subsequently focusing attention to them.
Mattout, A, Aaronson Y, Sailaja B S, Raghu Ram EV, Harikumar A, Mallm J-P, Sim K H, Nissim-Rafinia M, Supper E, Singh PB et al..  2015.  Heterochromatin Protein 1β (HP1β) has distinct functions and distinct nuclear distribution in pluripotent versus differentiated cells.. Genome biology. 16:213. Abstract
Pluripotent embryonic stem cells (ESCs) have the unique ability to differentiate into every cell type and to self-renew. These characteristics correlate with a distinct nuclear architecture, epigenetic signatures enriched for active chromatin marks and hyperdynamic binding of structural chromatin proteins. Recently, several chromatin-related proteins have been shown to regulate ESC pluripotency and/or differentiation, yet the role of the major heterochromatin proteins in pluripotency is unknown.
Ramaswamy, S, et al.  2015.  The neocortical microcircuit collaboration portal: a resource for rat somatosensory cortex.. Frontiers in neural circuits. 9:44.
Ankri, L, Husson Z, Pietrajtis K, Proville R, Léna C, Yarom Y, Dieudonné S, Uusisaari M Y.  2015.  A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity.. eLife. 4 Abstract
The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells.
Carmel, M S, Kahane N, Oberman F, Miloslavski R, Sela-Donenfeld D, Kalcheim C, Yisraeli JK.  2015.  A Novel Role for VICKZ Proteins in Maintaining Epithelial Integrity during Embryogenesis.. PloS one. 10(8):e0136408. Abstract
VICKZ (IGF2BP1,2,3/ZBP1/Vg1RBP/IMP1,2,3) proteins bind RNA and help regulate many RNA-mediated processes. In the midbrain region of early chick embryos, VICKZ is expressed in the neural folds and along the basal surface of the neural epithelium, but, upon neural tube closure, is down-regulated in prospective cranial neural crest (CNC) cells, concomitant with their emigration and epithelial-to-mesenchymal transition (EMT). Electroporation of constructs that modulate cVICKZ expression demonstrates that this down-regulation is both necessary and sufficient for CNC EMT. These results suggest that VICKZ down-regulation in CNC cell-autonomously promotes EMT and migration. Reduction of VICKZ throughout the embryo, however, inhibits CNC migration non-cell-autonomously, as judged by transplantation experiments in Xenopus embryos.
Busche, M A, Kekuš M, Adelsberger H, Noda T, Förstl H, Nelken I, Konnerth A.  2015.  Rescue of long-range circuit dysfunction in Alzheimer's disease models.. Nature Neuroscience. Abstract
Alzheimer's disease (AD) is associated with defects of synaptic connectivity. Such defects may not be restricted to local neuronal interactions but may extend to long-range brain activities, such as slow-wave oscillations that are particularly prominent during non-rapid eye movement (non-REM) sleep and are important for integration of information across distant brain regions involved in memory consolidation. There is increasing evidence that sleep is often impaired in AD, but it is unclear whether this impairment is directly related to amyloid-β (Aβ) pathology. Here we demonstrate that slow-wave activity is severely altered in the neocortex, thalamus and hippocampus in mouse models of AD amyloidosis. Most notably, our results reveal an Aβ-dependent impairment of slow-wave propagation, which causes a breakdown of the characteristic long-range coherence of slow-wave activity. The finding that the impairment can be rescued by enhancing GABAAergic inhibition identifies a synaptic mechanism underlying Aβ-dependent large-scale circuit dysfunction.
Jaffe-Dax, S, Raviv O, Jacoby N, Loewenstein Y, Ahissar M.  2015.  A Computational Model of Implicit Memory Captures Dyslexics' Perceptual Deficits. The Journal of Neuroscience. 35:12116–12126. AbstractPDF
Dyslexics are diagnosed for their poor reading skills, yet they characteristically also suffer from poor verbal memory and often from poor auditory skills. To date, this combined profile has been accounted for in broad cognitive terms. Here we hypothesize that the perceptual deficits associated with dyslexia can be understood computationally as a deficit in integrating prior information with noisy observations. To test this hypothesis we analyzed the performance of human participants in an auditory discrimination task using a two-parameter computational model. One parameter captures the internal noise in representing the current event, and the other captures the impact of recently acquired prior information. Our findings show that dyslexics' perceptual deficit can be accounted for by inadequate adjustment of these components; namely, low weighting of their implicit memory of past trials relative to their internal noise. Underweighting the stimulus statistics decreased dyslexics' ability to compensate for noisy observations. ERP measurements (P2 component) while participants watched a silent movie indicated that dyslexics' perceptual deficiency may stem from poor automatic integration of stimulus statistics. This study provides the first description of a specific computational deficit associated with dyslexia. SIGNIFICANCE STATEMENT This study presents the first attempt to specify the mechanisms underlying dyslexics' perceptual difficulties computationally by applying a specific model, inspired by the Bayesian framework. This model dissociates between the contribution of sensory noise and that of the prior statistics in an auditory perceptual decision task. We show that dyslexics cannot compensate for their perceptual noise by incorporating prior information. By contrast, adequately reading controls' usage of previous information is often close to optimal. We used ERP measurements to assess the neuronal stage of this deficit. We found that unlike their peers, dyslexics' ERP responses are not sensitive to the relations between the current observation and the prior observation, indicating that they cannot establish a reliable prior.
Loewenstein, Y, Yanover U, Rumpel S.  2015.  Predicting the Dynamics of Network Connectivity in the Neocortex. The Journal of Neuroscience. 35(36):12535–12544. AbstractPDF
Dynamic remodeling of connectivity is a fundamental feature of neocortical circuits. Unraveling the principles underlying these dynamics is essential for the understanding of how neuronal circuits give rise to computations. Moreover, as complete descriptions of the wiring diagram in cortical tissues are becoming available, deciphering the dynamic elements in these diagrams is crucial for relating them to cortical function. Here, we used chronic in vivo two-photon imaging to longitudinally follow a few thousand dendritic spines in the mouse auditory cortex to study the determinants of these spines' lifetimes. We applied nonlinear regression to quantify the independent contribution of spine age and several morphological parameters to the prediction of the future survival of a spine. We show that spine age, size, and geometry are parameters that can provide independent contributions to the prediction of the longevity of a synaptic connection. In addition, we use this framework to emulate a serial sectioning electron microscopy experiment and demonstrate how incorporation of morphological information of dendritic spines from a single time-point allows estimation of future connectivity states. The distinction between predictable and nonpredictable connectivity changes may be used in the future to identify the specific adaptations of neuronal circuits to environmental changes. The full dataset is publicly available for further analysis. SIGNIFICANCE STATEMENT The neural architecture in the neocortex exhibits constant remodeling. The functional consequences of these modifications are poorly understood, in particular because the determinants of these changes are largely unknown. Here, we aimed to identify those modifications that are predictable from current network state. To that goal, we repeatedly imaged thousands of dendritic spines in the auditory cortex of mice to assess the morphology and lifetimes of synaptic connections. We developed models based on morphological features of dendritic spines that allow predicting future turnover of synaptic connections. The dynamic models presented in this paper provide a quantitative framework for adding putative temporal dynamics to the static description of a neuronal circuit from single time-point connectomics experiments.
Mohan H, et al.  2015.  Dendritic and Axonal Architecture of Individual Pyramidal Neurons across Layers of Adult Human Neocortex. Cerebral Cortex. Abstract
The size and shape of dendrites and axons are strong determinants of neuronal information processing. Our knowledge on neuronal structure and function is primarily based on brains of laboratory animals. Whether it translates to human is not known since quantitative data on "full" human neuronal morphologies are lacking. Here, we obtained human brain tissue during resection surgery and reconstructed basal and apical dendrites and axons of individual neurons across all cortical layers in temporal cortex (Brodmann area 21). Importantly, morphologies did not correlate to etiology, disease severity, or disease duration. Next, we show that human L(ayer) 2 and L3 pyramidal neurons have 3-fold larger dendritic length and increased branch complexity with longer segments compared with temporal cortex neurons from macaque and mouse. Unsupervised cluster analysis classified 88% of human L2 and L3 neurons into human-specific clusters distinct from mouse and macaque neurons. Computational modeling of passive electrical properties to assess the functional impact of large dendrites indicates stronger signal attenuation of electrical inputs compared with mouse. We thus provide a quantitative analysis of "full" human neuron morphologies and present direct evidence that human neurons are not "scaled-up" versions of rodent or macaque neurons, but have unique structural and functional properties.
Deschamps, I, Agmon G, Loewenstein Y, Grodzinsky Y.  2015.  The processing of polar quantifiers, and numerosity perception. Cognition. 143:115-128. AbstractPDF
We investigated the course of language processing in the context of a verification task that required numerical estimation and comparison. Participants listened to sentences with complex quantifiers that contrasted in Polarity, a logical property (e.g., more-than-half, less-than-half), and then performed speeded verification on visual scenarios that displayed a proportion between 2 discrete quantities. We varied systematically not only the sentences, but also the visual materials, in order to study their effect on the verification process. Next, we used the same visual scenarios with analogous non-verbal probes that featured arithmetical inequality symbols (<, >). This manipulation enabled us to measure not only Polarity effects, but also, to compare the effect of different probe types (linguistic, non-linguistic) on processing. Like many previous studies, our results demonstrate that perceptual difficulty affects error rate and reaction time in keeping with Weber’s Law. Interestingly, these performance parameters are also affected by the Polarity of the quantifiers used, despite the fact that sentences had the exact same meaning, sentence structure, number of words, syllables, and temporal structure. Moreover, an analogous contrast between the non-linguistic probes (<, >) had no effect on performance. Finally, we observed no interaction between performance parameters governed by Weber’s Law and those affected by Polarity. We consider 4 possible accounts of the results (syntactic, semantic, pragmatic, frequency-based), and discuss their relative merit.
Marc, D, Hagai B.  2015.  Striatal cholinergic interneurons and cortico-striatal synaptic plasticity in health and disease. Movement Disorder. 3(no 8):1014-1025. Abstract
Basal ganglia disorders such as Parkinson's disease, dystonia, and Huntington's disease are characterized by a dysregulation of the basal ganglia neuromodulators (dopamine, acetylcholine, and others), which impacts cortico-striatal transmission. Basal ganglia disorders are often associated with an imbalance between the midbrain dopaminergic and striatal cholinergic systems. In contrast to the extensive research and literature on the consequences of a malfunction of midbrain dopaminergic signaling on the plasticity of the cortico-striatal synapse, very little is known about the role of striatal cholinergic interneurons in normal and pathological control of cortico-striatal transmission. In this review, we address the functional role of striatal cholinergic interneurons, also known as tonically active neurons and attempt to understand how the alteration of their functional properties in basal ganglia disorders leads to abnormal cortico-striatal synaptic plasticity. Specifically, we suggest that striatal cholinergic interneurons provide a permissive signal, which enables long-term changes in the efficacy of the cortico-striatal synapse. We further discuss how modifications in the striatal cholinergic activity pattern alter or prohibit plastic changes of the cortico-striatal synapse. Long-term cortico-striatal synaptic plasticity is the cellular substrate of procedural learning and adaptive control behavior. Hence, abnormal changes in this plasticity may underlie the inability of patients with basal ganglia disorders to adjust their behavior to situational demands. Normalization of the cholinergic modulation of cortico-striatal synaptic plasticity may be considered as a critical feature in future treatments of basal ganglia disorders.
Shteingart, H, Loewenstein Y.  2015.  The Effect of Sample Size and Cognitive Strategy on Probability Estimation Bias. Decison. 2(2):107-117. AbstractPDF
Probability estimation is an essential cognitive function in perception, motor control, and decision making. Many studies have shown that when making decisions in a stochastic operant conditioning task, people and animals behave as if they underesti- mate the probability of rare events. It is commonly assumed that this behavior is a natural consequence of estimating a probability from a small sample, also known as sampling bias. The objective of this article is to challenge this common lore. We show that, in fact, probabilities estimated from a small sample can lead to behaviors that will be interpreted as underestimating or as overestimating the probability of rare events, depending on the cognitive strategy used. Moreover, this sampling bias hypothesis makes an implausible prediction that minute differences in the values of the sample size or the underlying probability will determine whether rare events will be underweighted or overweighed. We discuss the implications of this sensitivity for the design and interpretation of experiments. Finally, we propose an alternative sequential learning model with a resetting of initial conditions for probability estimation and show that this model predicts the experimentally observed robust underweighting of rare events.
Ramirez de Noriega Fernando, Renana E, Odeya M, Lavi A, Eduard L, Hagai B, Zvi I.  2015.  Constant Current versus Constant Voltage Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Deisease. Stereotactic Functional Neurosurgry. 18(93(2)):114-121. Abstract
Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) is an established therapy for advanced Parkinson's disease (PD). Motor efficacy and safety have been established for constant voltage (CV) devices and more recently for constant current (CC) devices. CC devices adjust output voltage to provide CC stimulation irrespective of impedance fluctuation, while the current applied by CV stimulation depends on the impedance that may change over time. No study has directly compared the clinical effects of these two stimulation modalities. Objective: To compare the safety and clinical impact of CC STN DBS to CV STN DBS in patients with advanced PD 2 years after surgery. Methods: Patients were eligible for inclusion if they had undergone STN DBS surgery for idiopathic PD, had been implanted with a Medtronic Activa PC and if their stimulation program and medication had been stable for at least 1 year. This single-center trial was designed as a double-blind, randomized, prospective study with crossover after 2 weeks. Motor equivalence of the 2 modalities was confirmed utilizing part III of the Unified Parkinson's Disease Rating Scale (UPDRS). PD diaries and multiple subjective and objective evaluations of quality of life, depression, cognition and emotional processing were evaluated on both CV and on CC stimulation. Analysis using the paired t test with Bonferroni correction for multiple comparisons was performed to identify any significant difference between the stimulation modalities. Results: 8 patients were recruited (6 men, 2 women); 1 patient did not complete the study. The average age at surgery was 56.7 years (range 47-63). Disease duration at the time of surgery was 7.5 years (range 3-12). Patients were recruited 23.8 months (range 22.5-24) after surgery. At the postoperative study baseline, this patient group showed an average motor improvement of 69% (range 51-97) as measured by the change in UPDRS part III with stimulation alone. Levodopa equivalent medication was reduced on average by 67% (range 15-88). Patients were poorly compliant with PD diaries, and these did not yield useful information. The minor deterioration in quality-of-life scores (Parkinson's Disease Questionnaire-39, Quality of Life Enjoyment and Satisfaction Questionnaire) with CC stimulation were not statistically significant. Two measures of depression (Hamilton Rating Scale D17, Quick Inventory of Depressive Symptomatology - Self-Report) showed a nonsignificant lower score (less depression) with CC stimulation, but a third (Beck Depression Inventory) showed equivalence. Cognitive testing (Mini Mental State Examination) and emotional processing (Montreal Affective Voices) were equivalent for CC and CV. Conclusion: CC STN DBS is safe. For equivalent motor efficacy, no significant difference could be identified between CC and CV stimulation for nonmotor evaluations in PD patients 2 years after surgery.
Habib, N, Heidenreich M, Banerjee A, Habib N, Li Y, Trombetta J, Sur M, Zhang F.  2015.  In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9. Nat Biotechnol. Abstract
Probing gene function in the mammalian brain can be greatly assisted with methods to manipulate the genome of neurons in vivo. The clustered, regularly interspaced, short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) can be used to edit single or multiple genes in replicating eukaryotic cells, resulting in frame-shifting insertion/deletion (indel) mutations and subsequent protein depletion. Here, we delivered SpCas9 and guide RNAs using adeno-associated viral (AAV) vectors to target single (Mecp2) as well as multiple genes (Dnmt1, Dnmt3a and Dnmt3b) in the adult mouse brain in vivo. We characterized the effects of genome modifications in postmitotic neurons using biochemical, genetic, electrophysiological and behavioral readouts. Our results demonstrate that AAV-mediated SpCas9 genome editing can enable reverse genetic studies of gene function in the brain.
Santi, A, Friederici A, Makuuchi M, Grodzinsky Y.  2015.  An fMRI study dissociating distance measures computed by Broca's area in movement processing: clause boundary vs. identity.. Frontiers in Psychology. Abstract
http://journal.frontiersin.org/article/10.3389/fpsyg.2015.00654/abstract
Applebaum, M, Kalcheim C.  2015.  Mechanisms of myogenic specification and patterning. In: Vertebrate myogenesis, Stem cells and precursors. Series “Results and Problems in Cell Differentiation”. 56:77-98
Deschamps, I, Agmon G, Loewenstein Y, Grodzinsky Y.  2015.  The Processing of Polar Quantifiers, and Numerosity Perception. Cognition. 143:115-128.deschamps_et_al_cog_2015.pdf
Elyada, YM, Mizrahi A.  2015.  Becoming a mother — circuit plasticity underlying maternal behavior. Current Opinion in Neurobiology. 35:49-56.
Rothschild, G, Mizrahi A.  2015.  Global Order and Local Disorder in Brain Maps. Annual Review of Neuroscience. 38:null.
Cohen, L, Mizrahi A.  2015.  Plasticity during Motherhood: Changes in Excitatory and Inhibitory Layer 2/3 Neurons in Auditory Cortex. The Journal of Neuroscience. 35:1806-1815. Abstract
Maternal behavior can be triggered by auditory and olfactory cues originating from the newborn. Here we report how the transition to motherhood affects excitatory and inhibitory neurons in layer 2/3 (L2/3) of the mouse primary auditory cortex. We used in vivo two-photon targeted cell-attached recording to compare the response properties of parvalbumin-expressing neurons (PVNs) and pyramidal glutamatergic neurons (PyrNs). The transition to motherhood shifts the average best frequency of PVNs to higher frequency by a full octave, with no significant effect on average best frequency of PyrNs. The presence of pup odors significantly reduced the spontaneous and evoked activity of PVN. This reduction of feedforward inhibition coincides with a complimentary increase in spontaneous and evoked activity of PyrNs. The selective shift of PVN frequency tuning should render pup odor-induced disinhibition more effective for high-frequency stimuli, such as ultrasonic vocalizations. Indeed, pup odors increased neuronal responses of PyrNs to pup ultrasonic vocalizations. We conclude that plasticity in the mothers is mediated, at least in part, via modulation of the feedforward inhibition circuitry in the auditory cortex.