Modulation of Aversive Memory by Adult Hippocampal Neurogenesis.

Adult hippocampal neurogenesis (AHN) occurs in humans and every other mammalian species examined. Evidence that AHN is stimulated by a variety of treatments and behaviors with anxiolytic properties has sparked interest in harnessing AHN to treat anxiety disorders. However, relatively little is known about the mechanisms through which AHN modulates fear and anxiety.

Perisomatic changes in h-channels regulate depressive behaviors following chronic unpredictable stress.

Chronic stress can be a precipitating factor in the onset of depression. Lentiviral-mediated knockdown of HCN1 protein expression and reduction of functional I produce antidepressant behavior. However, whether h-channels are altered in an animal model of depression is not known.

Increased transient Na conductance and action potential output in layer 2/3 prefrontal cortex neurons of the fmr1 mouse.

Key Points: Layer 2/3 neurons of the prefrontal cortex display higher gain of somatic excitability, responding with a higher number of action potentials for a given stimulus, in fmr1 mice. In fmr1 L2/3 neurons, action potentials are taller, faster and narrower. Outside-out patch clamp recordings revealed that the maximum Na conductance density is higher in fmr1 L2/3 neurons.

Dendritic GIRK Channels Gate the Integration Window, Plateau Potentials, and Induction of Synaptic Plasticity in Dorsal But Not Ventral CA1 Neurons.

Studies comparing neuronal activity at the dorsal and ventral poles of the hippocampus have shown that the scale of spatial information increases and the precision with which space is represented declines from the dorsal to ventral end. These dorsoventral differences in neuronal output and spatial representation could arise due to differences in computations performed by dorsal and ventral CA1 neurons. In this study, we tested this hypothesis by quantifying the differences in dendritic integration and synaptic plasticity between dorsal and ventral CA1 pyramidal neurons of rat hippocampus.

International Union of Basic and Clinical Pharmacology. C. Nomenclature and Properties of Calcium-Activated and Sodium-Activated Potassium Channels.

A subset of potassium channels is regulated primarily by changes in the cytoplasmic concentration of ions, including calcium, sodium, chloride, and protons. The eight members of this subfamily were originally all designated as calcium-activated channels. More recent studies have clarified the gating mechanisms for these channels and have documented that not all members are sensitive to calcium.

CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory.

Although the role of CCR5 in immunity and in HIV infection has been studied widely, its role in neuronal plasticity, learning and memory is not understood. Here, we report that decreasing the function of CCR5 increases MAPK/CREB signaling, long-term potentiation (LTP), and hippocampus-dependent memory in mice, while neuronal CCR5 overexpression caused memory deficits. Decreasing CCR5 function in mouse barrel cortex also resulted in enhanced spike timing dependent plasticity and consequently, dramatically accelerated experience-dependent plasticity.

Prefrontal Single-Neuron Responses after Changes in Task Contingencies during Trace Eyeblink Conditioning in Rabbits.

A number of studies indicate that the medial prefrontal cortex (mPFC) plays a role in mediating the expression of behavioral responses during tasks that require flexible changes in behavior. During trace eyeblink conditioning, evidence suggests that the mPFC provides the cerebellum with a persistent input to bridge the temporal gap between conditioned and unconditioned stimuli. Therefore, the mPFC is in a position to directly mediate the expression of trace conditioned responses.

Computational principles of memory.

The ability to store and later use information is essential for a variety of adaptive behaviors, including integration, learning, generalization, prediction and inference. In this Review, we survey theoretical principles that can allow the brain to construct persistent states for memory. We identify requirements that a memory system must satisfy and analyze existing models and hypothesized biological substrates in light of these requirements.

Multisensory decisions provide support for probabilistic number representations.

A large body of evidence suggests that an approximate number sense allows humans to estimate numerosity in sensory scenes. This ability is widely observed in humans, including those without formal mathematical training. Despite this, many outstanding questions remain about the nature of the numerosity representation in the brain.

Analyzing single-molecule time series via nonparametric Bayesian inference.

The ability to measure the properties of proteins at the single-molecule level offers an unparalleled glimpse into biological systems at the molecular scale. The interpretation of single-molecule time series has often been rooted in statistical mechanics and the theory of Markov processes. While existing analysis methods have been useful, they are not without significant limitations including problems of model selection and parameter nonidentifiability.

Synaptic clustering within dendrites: an emerging theory of memory formation.

It is generally accepted that complex memories are stored in distributed representations throughout the brain, however the mechanisms underlying these representations are not understood. Here, we review recent findings regarding the subcellular mechanisms implicated in memory formation, which provide evidence for a dendrite-centered theory of memory. Plasticity-related phenomena which affect synaptic properties, such as synaptic tagging and capture, synaptic clustering, branch strength potentiation and spinogenesis provide the foundation for a model of memory storage that relies heavily on processes operating at the dendrite level.

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.

Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes.

Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning.

Persistent spiking in response to a discrete stimulus is considered to reflect the active maintenance of a memory for that stimulus until a behavioral response is made. This response pattern has been reported in learning paradigms that impose a temporal gap between stimulus presentation and behavioral response, including trace eyeblink conditioning. However, it is unknown whether persistent responses are acquired as a function of learning or simply represent an already existing category of response type.

A model of grid cell development through spatial exploration and spike time-dependent plasticity.

Grid cell responses develop gradually after eye opening, but little is known about the rules that govern this process. We present a biologically plausible model for the formation of a grid cell network. An asymmetric spike time-dependent plasticity rule acts upon an initially unstructured network of spiking neurons that receive inputs encoding animal velocity and location.

Determination of parameter identifiability in nonlinear biophysical models: A Bayesian approach.

A major goal of biophysics is to understand the physical mechanisms of biological molecules and systems. Mechanistic models are evaluated based on their ability to explain carefully controlled experiments. By fitting models to data, biophysical parameters that cannot be measured directly can be estimated from experimentation.

Decoding the brain's algorithm for categorization from its neural implementation.

Acts of cognition can be described at different levels of analysis: what behavior should characterize the act, what algorithms and representations underlie the behavior, and how the algorithms are physically realized in neural activity [1]. Theories that bridge levels of analysis offer more complete explanations by leveraging the constraints present at each level [2-4]. Despite the great potential for theoretical advances, few studies of cognition bridge levels of analysis.

Persistent activity in prefrontal cortex during trace eyelid conditioning: dissociating responses that reflect cerebellar output from those that do not.

Persistent neural activity, responses that outlast the stimuli that evoke them, plays an important role in neural computations and possibly in processes, such as working memory. Recent studies suggest that trace eyelid conditioning, which involves a temporal gap between the conditioned and unconditioned stimuli (the trace interval), requires persistent neural activity in a region of medial prefrontal cortex (mPFC). This persistent activity, which could be conveyed to cerebellum via a pathway through pons, may engage the cerebellum and allow for the expression of conditioned responses.

The long-term structural plasticity of cerebellar parallel fiber axons and its modulation by motor learning.

Presynaptic axonal varicosities, like postsynaptic spines, are dynamically added and eliminated even in mature neuronal circuitry. To study the role of this axonal structural plasticity in behavioral learning, we performed two-photon in vivo imaging of cerebellar parallel fibers (PFs) in adult mice. PFs make excitatory synapses on Purkinje cells (PCs) in the cerebellar cortex, and long-term potentiation and depression at PF-PC synapses are thought to play crucial roles in cerebellar-dependent learning.

Quantifying the internal structure of categories using a neural typicality measure.

How categories are represented continues to be hotly debated across neuroscience and psychology. One topic that is central to cognitive research on category representation but underexplored in neurobiological research concerns the internal structure of categories. Internal structure refers to how the natural variability between-category members is coded so that we are able to determine which members are more typical or better examples of their category.

mTOR Inhibition ameliorates cognitive and affective deficits caused by Disc1 knockdown in adult-born dentate granule neurons.

Abnormalities during brain development are thought to cause psychiatric illness and other neurodevelopmental disorders. However, developmental processes such as neurogenesis continue in restricted brain regions of adults, and disruptions of these processes could contribute to the phenotypes of neurodevelopmental disorders. As previously reported, we show that Disc1 knockdown specifically in adult-born dentate gyrus (DG) neurons results in increased mTOR signaling, hyperexcitability, and neuronal structure deficits.

A subtraction mechanism of temporal coding in cerebellar cortex.

The temporally specific learning displayed by the cerebellum facilitates mechanistic analysis of neural timing and temporal coding. We report evidence for a subtraction-like mechanism of temporal coding in cerebellar cortex in which activity in a subset of granule cells specifically codes the interval between the offset of two mossy fiber inputs. In a large-scale cerebellar simulation, cessation of one of two ongoing mossy fiber inputs produces a robust temporal code in the population of granule cells.

Normal eye-specific patterning of retinal inputs to murine subcortical visual nuclei in the absence of brain-derived neurotrophic factor.

Brain-derived neurotrophic factor (BDNF) is a preferred ligand for a member of the tropomyosin-related receptor family, trkB. Activation of trkB is implicated in various activity-independent as well as activity-dependent growth processes in many developing and mature neural systems. In the subcortical visual system, where electrical activity has been implicated in normal development, both differential survival, as well as remodeling of axonal arbors, have been suggested to contribute to eye-specific segregation of retinal ganglion cell inputs.

Role for A kinase-anchoring proteins (AKAPS) in glutamate receptor trafficking and long term synaptic depression.

Expression of N-methyl d-aspartate (NMDA) receptor-dependent homosynaptic long term depression at synapses in the hippocampus and neocortex requires the persistent dephosphorylation of postsynaptic protein kinase A substrates. An attractive mechanism for expression of long term depression is the loss of surface AMPA (alpha-amino-3-hydroxy-5-methylisoxazale-4-propionate) receptors at synapses. Here we show that a threshold level of NMDA receptor activation must be exceeded to trigger a stable loss of AMPA receptors from the surface of cultured hippocampal neurons.

Enhancement of synaptic plasticity through chronically reduced Ca2+ flux during uncorrelated activity.

The plasticity of synapses within neural circuits is regulated by activity, but the underlying mechanisms remain elusive. Using the dye FM1-43 to directly image presynaptic function, we found that large numbers of presynaptic terminals in hippocampal cultures have a low release probability. While these terminals were not readily modifiable, a transient but not permanent long-term reduction of network activity or Ca2+ influx could increase their modifiability.