The Neurosciences Institute

San Diego, CA, United States

The Neurosciences Institute

San Diego, CA, United States
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Schwartze M.,Max Planck Institute for Human Cognitive and Brain Sciences | Keller P.E.,Max Planck Institute for Human Cognitive and Brain Sciences | Patel A.D.,The Neurosciences Institute | Kotz S.A.,Max Planck Institute for Human Cognitive and Brain Sciences
Behavioural Brain Research | Year: 2011

The basal ganglia (BG) are part of extensive subcortico-cortical circuits that are involved in a variety of motor and non-motor cognitive functions. Accumulating evidence suggests that one specific function that engages the BG and associated cortico-striato-thalamo-cortical circuitry is temporal processing, i.e., the mechanisms that underlie the encoding, decoding and evaluation of temporal relations or temporal structure. In the current study we investigated the interplay of two processes that require precise representations of temporal structure, namely the perception of an auditory pacing signal and manual motor production by means of finger tapping in a sensorimotor synchronization task. Patients with focal lesions of the BG and healthy control participants were asked to align finger taps to tone sequences that either did or did not contain a tempo acceleration or tempo deceleration at a predefined position, and to continue tapping at the final tempo after the pacing sequence had ceased. Performance in this adaptive synchronization-continuation paradigm differed between the two groups. Selective damage to the BG affected the abilities to detect tempo changes and to perform attention-dependent error correction, particularly in response to tempo decelerations. An additional assessment of preferred spontaneous, i.e., unpaced but regular, production rates yielded more heterogeneous results in the patient group. Together these findings provide evidence for less efficient processing in the perception and the production of temporal structure in patients with focal BG lesions. The results also support the functional role of the BG system in attention-dependent temporal processing. © 2010 Elsevier B.V.


Walcott E.C.,The Neurosciences Institute | Higgins E.A.,The Neurosciences Institute | Desai N.S.,The Neurosciences Institute
Journal of Neuroscience | Year: 2011

Valproic acid (VPA) is among the most teratogenic of commonly prescribed anticonvulsants, increasing the risk in humans of major malformations and impaired cognitive development. Likewise, rats exposed prenatally to VPA exhibit a variety of neuroanatomical and behavioral abnormalities. Previous work has shown that pyramidal neuron physiology in young VPA-exposed animalsis markedby two strong abnormalities: an impairment in intrinsic neuronal excitability and an increase in NMDA synaptic currents. In this study, we investigated these abnormalities across postnatal development using whole-cell patch recordings from layer 2/3 neurons of medial prefrontal cortex. We found that both abnormalities were at a peak soon after birth but were gradually corrected as animals matured, to the extent that normal excitability and NMDA currents had been restored by early adolescence. The manner in which this correction happened suggested coordination between the two processes. Using computational models fittedtothe physiological data,weargue that the two abnormalities trade off against each other, with the effects on network activity of the one balancing the effects of the other. This may constitute part of the nervous system's homeostatic response to teratogenic insult: an attemptto maintain stability despite a strong challenge. © 2011 the authors.


Bregman M.R.,University of California at San Diego | Patel A.D.,The Neurosciences Institute | Gentner T.Q.,University of California at San Diego
Cognition | Year: 2012

Songbirds and humans share many parallels in vocal learning and auditory sequence processing. However, the two groups differ notably in their abilities to recognize acoustic sequences shifted in absolute pitch (pitch height). Whereas humans maintain accurate recognition of words or melodies over large pitch height changes, songbirds are comparatively much poorer at recognizing pitch-shifted tone sequences. This apparent disparity may reflect fundamental differences in the neural mechanisms underlying the representation of sound in songbirds. Alternatively, because non-human studies have used sine-tone stimuli almost exclusively, tolerance to pitch height changes in the context of natural signals may be underestimated. Here, we show that European starlings, a species of songbird, can maintain accurate recognition of the songs of other starlings when the pitch of those songs is shifted by as much as ±40%. We observed accurate recognition even for songs pitch-shifted well outside the range of frequencies used during training, and even though much smaller pitch shifts in conspecific songs are easily detected. With similar training using human piano melodies, recognition of the pitch-shifted melodies is very limited. These results demonstrate that non-human pitch processing is more flexible than previously thought and that the flexibility in pitch processing strategy is stimulus dependent. © 2011 Elsevier B.V.


Zheng W.,The Neurosciences Institute
Frontiers in Systems Neuroscience | Year: 2012

Behavioral adaption to a changing environment is critical for an animal's survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment. © 2012 Zheng.


Zheng W.,The Neurosciences Institute
Frontiers in Systems Neuroscience | Year: 2012

Behavioral adaption to a changing environment is critical for an animal's survival. How well the brain can modify its functional properties based on experience essentially defines the limits of behavioral adaptation. In adult animals the extent to which experience shapes brain function has not been fully explored. Moreover, the perceptual consequences of experience-induced changes in the brains of adults remain unknown. Here we show that the tonotopic map in the primary auditory cortex of adult rats living with low-level ambient noise underwent a dramatic reorganization. Behaviorally, chronic noise-exposure impaired fine, but not coarse pitch discrimination. When tested in a noisy environment, the noise-exposed rats performed as well as in a quiet environment whereas the control rats performed poorly. This suggests that noise-exposed animals had adapted to living in a noisy environment. Behavioral pattern analyses revealed that stress or distraction engendered by the noisy background could not account for the poor performance of the control rats in a noisy environment. A reorganized auditory map may therefore have served as the neural substrate for the consistent performance of the noise-exposed rats in a noisy environment. © 2012 Zheng.


Edelman G.M.,The Neurosciences Institute | Gally J.A.,The Neurosciences Institute
Frontiers in Integrative Neuroscience | Year: 2013

Reentry in nervous systems is the ongoing bidirectional exchange of signals along reciprocal axonal fibers linking two or more brain areas. The hypothesis that reentrant signaling serves as a general mechanism to couple the functioning of multiple areas of the cerebral cortex and thalamus was first proposed in 1977 and 1978 (Edelman, 1978). A review of the amount and diversity of supporting experimental evidence accumulated since then suggests that reentry is among the most important integrative mechanisms in vertebrate brains (Edelman, 1993). Moreover, these data prompt testable hypotheses regarding mechanisms that favor the development and evolution of reentrant neural architectures. © 2013 Edelman and Gally.


Chen Y.,The Neurosciences Institute
Frontiers in Computational Neuroscience | Year: 2017

Amajor function of central nervous systems is to discriminate different categories or types of sensory input. Neuronal networks accomplish such tasks by learning different sensory maps at several stages of neural hierarchy, such that different neurons fire selectively to reflect different internal or external patterns and states. The exact mechanisms of such map formation processes in the brain are not completely understood. Here we study the mechanism by which a simple recurrent/reentrant neuronal network accomplish group selection and discrimination to different inputs in order to generate sensory maps. We describe the conditions and mechanism of transition from a rhythmic epileptic state (in which all neurons fire synchronized and indiscriminately to any input) to a winner-take-all state in which only a subset of neurons fire for a specific input. We prove an analytic condition under which a stable bump solution and a winner-take-all state can emerge from the local recurrent excitation-inhibition interactions in a three-layer spiking network with distinct excitatory and inhibitory populations, and demonstrate the importance of surround inhibitory connection topology on the stability of dynamic patterns in spiking neural network. © 2017 Chen.


Madl T.,University of Vienna | Baars B.J.,The Neurosciences Institute | Franklin S.,University of Memphis
PLoS ONE | Year: 2011

We propose that human cognition consists of cascading cycles of recurring brain events. Each cognitive cycle senses the current situation, interprets it with reference to ongoing goals, and then selects an internal or external action in response. While most aspects of the cognitive cycle are unconscious, each cycle also yields a momentary "ignition" of conscious broadcasting. Neuroscientists have independently proposed ideas similar to the cognitive cycle, the fundamental hypothesis of the LIDA model of cognition. High-level cognition, such as deliberation, planning, etc., is typically enabled by multiple cognitive cycles. In this paper we describe a timing model LIDA's cognitive cycle. Based on empirical and simulation data we propose that an initial phase of perception (stimulus recognition) occurs 80-100 ms from stimulus onset under optimal conditions. It is followed by a conscious episode (broadcast) 200-280 ms after stimulus onset, and an action selection phase 60-110 ms from the start of the conscious phase. One cognitive cycle would therefore take 260-390 ms. The LIDA timing model is consistent with brain evidence indicating a fundamental role for a theta-gamma wave, spreading forward from sensory cortices to rostral corticothalamic regions. This posteriofrontal theta-gamma wave may be experienced as a conscious perceptual event starting at 200-280 ms post stimulus. The action selection component of the cycle is proposed to involve frontal, striatal and cerebellar regions. Thus the cycle is inherently recurrent, as the anatomy of the thalamocortical system suggests. The LIDA model fits a large body of cognitive and neuroscientific evidence. Finally, we describe two LIDA-based software agents: the LIDA Reaction Time agent that simulates human performance in a simple reaction time task, and the LIDA Allport agent which models phenomenal simultaneity within timeframes comparable to human subjects. While there are many models of reaction time performance, these results fall naturally out of a biologically and computationally plausible cognitive architecture. © 2011 Madl et al.


Chen S.,The Neurosciences Institute | Owens G.C.,The Neurosciences Institute | Makarenkova H.,The Neurosciences Institute | Edelman D.B.,The Neurosciences Institute
PLoS ONE | Year: 2010

Background: Tubulin is a major substrate of the cytoplasmic class II histone deacetylase HDAC6. Inhibition of HDAC6 results in higher levels of acetylated tubulin and enhanced binding of the motor protein kinesin-1 to tubulin, which promotes transport of cargoes along microtubules. Microtubule-dependent intracellular trafficking may therefore be regulated by modulating the activity of HDAC6. We have shown previously that the neuromodulator serotonin increases mitochondrial movement in hippocampal neurons via the Akt-GSK3β signaling pathway. Here, we demonstrate a role for HDAC6 in this signaling pathway. Methodology/Principal Findings: We found that the presence of tubacin, a specific HDAC6 inhibitor, dramatically enhanced mitochondrial movement in hippocampal neurons, whereas niltubacin, an inactive tubacin analog, had no effect. Compared to control cultures, higher levels of acetylated tubulin were found in neurons treated with tubacin, and more kinesin-1 was associated with mitochondria isolated from these neurons. Inhibition of GSK3β decreased cytoplasmic deacetylase activity and increased tubulin acetylation, whereas blockade of Akt, which phosphorylates and down-regulates GSK3β, increased cytoplasmic deacetylase activity and decreased tubulin acetylation. Concordantly, the administration of 5-HT, 8-OH-DPAT (a specific 5-HT1A receptor agonist), or fluoxetine (a 5-HT reuptake inhibitor) increased tubulin acetylation. GSK3β was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3β resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3β phosphorylation site in HDAC6. GSK3β may therefore regulate HDAC6 activity by phosphorylation. Conclusions/Significance: This study demonstrates that HDAC6 plays an important role in the modulation of mitochondrial transport. The link between HDAC6 and GSK3β, established here, has important implications for our understanding of neurodegenerative disorders. In particular, abnormal mitochondrial transport, which has been observed in such disorders as Alzheimer's disease and Parkinson's disease, could result from the misregulation of HDAC6 by GSK3β. HDAC6 may therefore constitute an attractive target in the treatment of these disorders. © 2010 Chen et al.


Patel A.D.,The Neurosciences Institute
Annals of the New York Academy of Sciences | Year: 2012

Recent research suggests that musical training enhances the neural encoding of speech. Why would musical training have this effect? The OPERA hypothesis proposes an answer on the basis of the idea that musical training demands greater precision in certain aspects of auditory processing than does ordinary speech perception. This paper presents two assumptions underlying this idea, as well as two clarifications, and suggests directions for future research. © 2012 New York Academy of Sciences..

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