Learning in deep neural networks and brains with similarity-weighted interleaved learning.

Understanding how the brain learns throughout a lifetime remains a long-standing challenge. In artificial neural networks (ANNs), incorporating novel information too rapidly results in catastrophic interference, i.e.

Early impairment of thalamocortical circuit activity and coherence in a mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive, fatal neurodegenerative disorder characterized by motor, cognitive, and psychiatric disturbances. There is no known cure for HD, but its progressive nature allows for early therapeutic intervention. Currently, much of the research has focused on the striatum, however, there is evidence suggesting that disruption of thalamocortical circuits could underlie some of the early symptoms of HD.

Selective Modulation of Orbitofrontal Network Activity during Negative Occasion Setting.

Discrete cues can gain powerful control over behavior to help an animal anticipate and cope with upcoming events. This is important in conditions where understanding the relationship between complex stimuli provides a means to resolving situational ambiguity. However, it is unclear how cortical circuits generate and maintain these signals that conditionally regulate behavior.

Parvalbumin Interneurons Modulate Striatal Output and Enhance Performance during Associative Learning.

The prevailing view is that striatal parvalbumin (PV)-positive interneurons primarily function to downregulate medium spiny projection neuron (MSN) activity via monosynaptic inhibitory signaling. Here, by combining in vivo neural recordings and optogenetics, we unexpectedly find that both suppressing and over-activating PV cells attenuates spontaneous MSN activity. To account for this, we find that, in addition to monosynaptic coupling, PV-MSN interactions are mediated by a competing disynaptic inhibitory circuit involving a variety of neuropeptide Y-expressing interneurons.

Differential Encoding of Time by Prefrontal and Striatal Network Dynamics.

Unlabelled: Telling time is fundamental to many forms of learning and behavior, including the anticipation of rewarding events. Although the neural mechanisms underlying timing remain unknown, computational models have proposed that the brain represents time in the dynamics of neural networks. Consistent with this hypothesis, changing patterns of neural activity dynamically in a number of brain areas-including the striatum and cortex-has been shown to encode elapsed time.

A shared neural ensemble links distinct contextual memories encoded close in time.

Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. According to the memory allocation hypothesis, learning triggers a temporary increase in neuronal excitability that biases the representation of a subsequent memory to the neuronal ensemble encoding the first memory, such that recall of one memory increases the likelihood of recalling the other memory. Here we show in mice that the overlap between the hippocampal CA1 ensembles activated by two distinct contexts acquired within a day is higher than when they are separated by a week.

Retrieval and Reconsolidation Accounts of Fear Extinction.

Extinction is the primary mode for the treatment of anxiety disorders. However, extinction memories are prone to relapse. For example, fear is likely to return when a prolonged time period intervenes between extinction and a subsequent encounter with the fear-provoking stimulus (spontaneous recovery).

Transforming growth factor β recruits persistent MAPK signaling to regulate long-term memory consolidation in Aplysia californica.

In this study, we explore the mechanistic relationship between growth factor signaling and kinase activity that supports the protein synthesis-dependent phase of long-term memory (LTM) consolidation for sensitization ofAplysia Specifically, we examine LTM for tail shock-induced sensitization of the tail-elicited siphon withdrawal (T-SW) reflex, a form of memory that requires both (i) extracellular signal-regulated kinase (ERK1/2; MAPK) activity within identified sensory neurons (SNs) that mediate the T-SW and (ii) the activation of transforming growth factor β (TGFβ) signaling. We now report that repeated tail shocks that induce intermediate-term (ITM) and LTM for sensitization, also induce a sustained post-training phase of MAPK activity in SNs (lasting at least 1 h). We identified two mechanistically distinct phases of post-training MAPK: (i) an immediate phase that does not require ongoing protein synthesis or TGFβ signaling, and (ii) a sustained phase that requires both protein synthesis and extracellular TGFβ signaling.

Brain activity mapping at multiple scales with silicon microprobes containing 1,024 electrodes.

The coordinated activity of neural ensembles across multiple interconnected regions has been challenging to study in the mammalian brain with cellular resolution using conventional recording tools. For instance, neural systems regulating learned behaviors often encompass multiple distinct structures that span the brain. To address this challenge we developed a three-dimensional (3D) silicon microprobe capable of simultaneously measuring extracellular spike and local field potential activity from 1,024 electrodes.

CREB regulates memory allocation in the insular cortex.

The molecular and cellular mechanisms of memory storage have attracted a great deal of attention. By comparison, little is known about memory allocation, the process that determines which specific neurons in a neural network will store a given memory. Previous studies demonstrated that memory allocation is not random in the amygdala; these studies showed that amygdala neurons with higher levels of the cyclic-AMP-response-element-binding protein (CREB) are more likely to be recruited into encoding and storing fear memory.

Synaptic tagging during memory allocation.

There is now compelling evidence that the allocation of memory to specific neurons (neuronal allocation) and synapses (synaptic allocation) in a neurocircuit is not random and that instead specific mechanisms, such as increases in neuronal excitability and synaptic tagging and capture, determine the exact sites where memories are stored. We propose an integrated view of these processes, such that neuronal allocation, synaptic tagging and capture, spine clustering and metaplasticity reflect related aspects of memory allocation mechanisms. Importantly, the properties of these mechanisms suggest a set of rules that profoundly affect how memories are stored and recalled.

Blood testing in sport: hematological profiling.

Hemoglobin concentration and percent reticulocytes (%retics) were analyzed in blood samples taken pre-competition, post-competition, and during out of competition testing in elite speed skaters. Percent reticulocytes during screening was not different from the values obtained post-race, and no significant gender difference was found. Mean hemoglobin concentration both in males and females was slightly higher at 1 425 m altitude compared to <750 m altitude (0.

Molecular and cellular approaches to memory allocation in neural circuits.

Although memory allocation is a subject of active research in computer science, little is known about how the brain allocates information within neural circuits. There is an extensive literature on how specific types of memory engage different parts of the brain, and how neurons in these regions process and store information. Until recently, however, the mechanisms that determine how specific cells and synapses within a neural circuit (and not their neighbors) are recruited during learning have received little attention.

Temporal phases of activity-dependent plasticity and memory are mediated by compartmentalized routing of MAPK signaling in aplysia sensory neurons.

An activity-dependent form of intermediate memory (AD-ITM) for sensitization is induced in Aplysia by a single tail shock that gives rise to plastic changes (AD-ITF) in tail sensory neurons (SNs) via the interaction of action potential firing in the SN coupled with the release of serotonin in the CNS. Activity-dependent long-term facilitation (AD-LTF, lasting >24hr) requires protein synthesis dependent persistent mitogen-activated protein kinase (MAPK) activation and translocation to the SN nucleus. We now show that the induction of the earlier temporal phase (AD-ITM and AD-ITF), which is translation and transcription independent, requires the activation of a compartmentally distinct novel signaling cascade that links second messengers, MAPK and PKC into a unified pathway within tail SNs.

Small G proteins exhibit pattern sensitivity in MAPK activation during the induction of memory and synaptic facilitation in Aplysia.

Memory formation is highly sensitive to specific patterns of training, but the cellular and molecular mechanisms underlying pattern sensitivity are not well understood. We explored this general question by using Aplysia californica as a model system. We examined the regulation of MAPK (ERK1/2) activation by small G proteins in the CNS by using different patterns of analog stimuli that mimic different patterns of behavioral training for memory induction.

Hemoglobin levels and athletic performance in elite speed skaters during the olympic season 2006.

Objective: To test the hypotheses that the hemoglobin (Hb) distribution curve in elite male and female long track speed skaters is not normally distributed and that there is a positive relationship between competitive success and Hb concentration.

Design: A venous blood sample was taken before the events from all skaters. The Hb concentration distribution curves of all ranked from 1 to 30 were tested for normality.

Intermediate-term processes in memory formation.

Neuroscientists have invested considerable effort in attempting to elucidate the molecular mechanisms that mediate short-term and long-term forms of learning and memory. For instance, the discovery of long-term potentiation inspired a field that has produced hundreds of studies examining both early and late forms of long-term potentiation. And at the behavioral level, most neuroscientists investigate either short- or long-term forms of memory or some combination of the two.

Hemoglobin level in elite speed skaters from 2000 up to 2005, and its relationship with competitive results.

We studied the mean hemoglobin (Hb) concentration in elite male and female long track junior and senior speed skaters from 2000 to 2005. In addition, the number of abnormal hematological findings observed over this period of time was investigated. We also studied whether there were differences in Hb concentration between top ranked and lower ranked skaters, and whether a relationship between Hb concentration and competitive results could be observed.

Molecular nodes in memory processing: insights from Aplysia.

Recent research in a variety of systems indicates that memory formation can involve the activation of a wide range of molecular cascades. In assessing this recent work it is clear that no single cascade is uniquely important for all forms of memory, nor is a single form of memory uniquely dependent on a single cascade. Rather, it appears that molecular networks are differentially engaged in the induction of various forms of memory.

Hemoglobin and hematocrit values after saline infusion and tourniquet.

This study attempted to contribute to standardization of blood testing in sport, and to investigate the effect of artificial dilution with saline. In 10 healthy, physically active males and 3 healthy physically active females hemoglobin (Hb), hematocrit (Ht), and % reticulocytes (%retics) were measured at different time points to look for possible fluctuations during day time, while the subjects had regular coffee breaks and lunch. In 7 of the subjects in a separate experiment 500 ml of saline were infused around 8 am and Hb, Ht, and %retics were measured before and every hour thereafter until 7 hours after infusion.

A hybrid fibronectin motif protein as an integrin targeting selective tumor vascular thrombogen.

Targeted thrombotic eradication of solid tumors is a novel therapeutic strategy. The feasibility, efficacy, selectivity, and safety are dependent on multiple variables of protein design, molecular assembly, vascular target, and exclusive restriction of function to the tumor vasculature. To advance this strategy, we describe a design of an integrin targeting selective tumor vascular thrombogen.

Intermediate-term memory for site-specific sensitization in aplysia is maintained by persistent activation of protein kinase C.

Recent studies of long-term synaptic plasticity and long-term memory have demonstrated that the same functional endpoint, such as long-term potentiation, can be induced through distinct signaling pathways engaged by different patterns of stimulation. A critical question raised by these studies is whether different induction pathways either converge onto a common molecular mechanism or engage different molecular cascades for the maintenance of long-term plasticity. We directly examined this issue in the context of memory for sensitization in the marine mollusk Aplysia.

Differential role of mitogen-activated protein kinase in three distinct phases of memory for sensitization in Aplysia.

The mitogen-activated protein kinase (MAPK) pathway has been implicated recently in synaptic plasticity and memory. Here we used tail shock-induced sensitization of the tail-elicited siphon withdrawal reflex in Aplysia to examine the role of MAPK in three different phases of memory. We show that a specific pattern of serotonin (5-HT) application that produces intermediate-term and long-term synaptic facilitation (ITF and LTF, respectively) of the sensory-motor (SN-MN) synapses in Aplysia leads to sustained activation of extracellular signal-regulated kinase in the ventrocaudal cluster sensory neurons (SNs), which include the tail SNs.