Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task

Single-unit recording studies of posterior parietal neurons have indicated a similarity of neuronal activation to that observed in the dorsolateral prefrontal cortex in relation to performance of delayed saccade tasks. A key issue addressed in the present study is whether the different classes of neuronal activity observed in these tasks are encountered more frequently in one or the other area or otherwise exhibit region-specific properties. The present study is the first to directly compare these patterns of neuronal activity by alternately recording from parietal area 7ip and prefrontal area 8a, under the identical behavioral conditions, within the same hemisphere of two monkeys performing an oculomotor delayed response task. The firing rate of 222 posterior parietal and 235 prefrontal neurons significantly changed during the cue, delay, and/or saccade periods of the task. Neuronal responses in the two areas could be distinguished only by subtle differences in their incidence and timing. Thus neurons responding to the cue appeared earliest and were more frequent among the task-related neurons within parietal cortex, whereas neurons exhibiting delay-period activity accounted for a larger proportion of task-related neurons in prefrontal cortex. Otherwise, the task-related neuronal activities were remarkably similar. Cue period activity in prefrontal and parietal cortex exhibited comparable spatial tuning and temporal duration characteristics, taking the form of phasic, tonic, or combined phasic/tonic excitation in both cortical populations. Neurons in both cortical areas exhibited sustained activity during the delay period with nearly identical spatial tuning. The various patterns of delay-period activity-tonic, increasing or decreasing, alone or in combination with greater activation during cue and/or saccade periods-likewise were distributed to both cortical areas. Finally, similarities in the two populations extended to the proportion and spatial tuning of presaccadic and postsaccadic neuronal activity occurring in relation to the memory-guided saccade. The present findings support and extend evidence for a faithful duplication of receptive field properties and virtually every other dimension of task-related activity observed when parietal and prefrontal cortex are recruited to a common task. This striking similarity attests to the principal that information shared by a prefrontal region and a sensory association area with which it is connected is domain specific and not subject to hierarchical elaboration, as is evident at earlier stages of visuospatial processing.     

Combined use of NMR, distance geometry and MD calculations for the conformational analysis of opioid peptides of the type [D(L)-Cys2, D(L)-Cys5]enkephalin

To understand the cellular processes involved in learning and memory, the cellular responses of neurons to calcium (Ca2+) signals, which can be evoked via synaptic activity, should be examined. A series of investigations in primary cultures of neurons revealed that the regulation of brain-derived neurotrophic factor (BDNF) mRNA expression is mediated by almost the same Ca2+ signaling pathways as that of c-fos mRNA expression. Such early co-activation of both genes in response to Ca2+ signals further suggests that sets of calcium-responsive genes (CaRGs) are concurrently activated by Ca2+ signals. The products encoded by CaRGs should then evoke a variety of physiological responses in neurons with the expression of another set of genes, the products of which are directly involved in the outcomes of neuronal functions. Thus, a cascade of gene expression can be induced by Ca2+ signals evoked via synaptic activity. It is of particular interest to identify the CaRGs and investigate the regulational mechanisms of their expression. A cellular approach using primary cultures of neurons would therefore lead to a better understanding of the intracellular processes involved in learning and memory.     

Spontaneous activity and recurrent inhibition in cultured hippocampal networks

As a model for an integrated neuronal network based on the concept of modular units, we have investigated the occurrence of spontaneous activity and the formation of synaptic circuits in primary cultures of dissociated hippocampal neurons from the embryonic rat. Sodium-dependent action potentials (APs) could be elicited after 1 day in vitro (DIV), whereas spontaneous postsynaptic potentials (PSPs), "miniature" PSPs and APs appeared after 3-6 DIV. The number of cells with spontaneous APs and the rate of APs increased during development of the neuritic network. In addition to a stochastic spike interval distribution, pyramid-shaped neurons could be identified after 10-12 DIV, which fired preferentially at interspike intervals between 20-120 ms and 190-400 ms. This distinctive bimodal interspike interval pattern was sensitive to GABA-A antagonists. Simultaneous recordings of pairs of neurons demonstrated recurrent inhibitory, GABA-ergic synaptic circuits. In addition, a subpopulation of GABAergic neurons could be visualized by immunocytochemistry. These results are discussed in relation to the hypothesis that spontaneous firing of connected neurons is network-driven, based on synaptic "noise" and patterned by recurrent inhibition.     

Filopodia and growth cones in the vertically migrating granule cells of the postnatal mouse cerebellum

The significance of cholinergic modulation for associative memory performance in the piriform cortex was examined in a study combining cellular neurophysiology in brain slices with realistic biophysical network simulations. Three different physiological effects of acetylcholine were identified at the single-cell level: suppression of neuronal adaptation, suppression of synaptic transmission in the intrinsic fibers layer, and activity-dependent increase in synaptic strength. Biophysical simulations show how these three effects are joined together to enhance learning and recall performance of the cortical network. Furthermore, our data suggest that activity-dependent synaptic decay during learning is a crucial factor in determining learning capability of the cortical network. Accordingly, it is predicted that acetylcholine should also enhance long-term depression in the piriform cortex.     

Effects of synaptic noise on a neuronal pool model with strong excitatory drive and recurrent inhibition

A model originally proposed by Akazawa and Kato (1990) for the spinal cord was adopted as prototypical of a neuronal pool with strong excitatory drive and strong recurrent inhibition. Our simulations of the model have shown that a strong synchronization occurs between the spike trains in the neuronal pool. This happens because the proposed model has a single and strong excitatory drive on the neuronal pool. However, usually a multitude of other randomly occurring synaptic inputs impinge on the neuronal pool and therefore a new investigation was carried out to study the effects of synaptic noise on the network behavior. The synaptic noise decreased the degree of synchronization of the neuronal spike trains but on the other hand caused an unexpected decrease in the mean firing rate of the neuronal pool. A detailed analysis indicated that this phenomenon is due to a combination of two mechanisms: a saturation of the feedback inhibition and a decrease of the synchronization in the neuronal pool with synaptic noise. The synaptic noise caused a more frequent activation of the saturated recurrent inhibitory feedback loop along time, thereby increasing the inhibitory effect on the neuronal pool.     

A neuronal network for computing population vectors in the leech

The correlation of neuronal activity with sensory input and behavioural output has revealed that information is often encoded in the activity of many neurons across a population, that is, a neural population code is used. The possible algorithms that downstream networks use to read out this population code have been studied by manipulating the activity of a few neurons in a population. We have used this approach to study population coding in a small network underlying the leech local bend, a body bend directed away from a touch stimulus. Because of the small size of this network we are able to monitor and manipulate the complete set of sensory inputs to the network. We show here that the population vector formed by the spike counts of the active mechanosensory neurons is well correlated with bend direction. A model based on the known connectivity of the identified neurons in the local bend network can account for our experimental results, and is suitable for reading out the neural population vector. Thus, for the first time to our knowledge, it is possible to link a proposed algorithm for neural population coding with synaptic and network mechanisms in an experimental system.     

Reward expectancy in primate prefrontal neurons

The prefrontal cortex is important in the organization of goal-directed behaviour. When animals are trained to work for a particular goal or reward, reward 'expectancy' is processed by prefrontal neurons. Recent studies of the prefrontal cortex have concentrated on the role of working memory in the control of behaviour. In spatial delayed-response tasks, neurons in the prefrontal cortex show activity changes during the delay period between presentation of the cue and the reward, with some of the neurons being spatially specific (that is, responses vary with the cue position). Here I report that the delay activity in prefrontal neurons is dependent also on the particular reward received for the behavioural response, and to the way the reward is given. It seems that the prefrontal cortex may monitor the outcome of goal-directed behaviour.     

Activity-dependent changes in the intrinsic properties of cultured neurons

Learning and memory arise through activity-dependent modifications of neural circuits. Although the activity dependence of synaptic efficacy has been studied extensively, less is known about how activity shapes the intrinsic electrical properties of neurons. Lobster stomatogastric ganglion neurons fire in bursts when receiving synaptic and modulatory input but fire tonically when pharmacologically isolated. Long-term isolation in culture changed their intrinsic activity from tonic firing to burst firing. Rhythmic stimulation reversed this transition through a mechanism that was mediated by a rise in intracellular calcium concentration. These data suggest that neurons regulate their conductances to maintain stable activity patterns and that the intrinsic properties of a neuron depend on its recent history of activation.     

Intrinsic and thalamic excitatory inputs onto songbird LMAN neurons differ in their pharmacological and temporal properties

In passerine songbirds, the lateral portion of the magnocellular nucleus of the anterior neostriatum (LMAN) plays a vital role in song learning, possibly by encoding sensory information and providing sensory feedback to the vocal motor system. Consistent with this, LMAN neurons are auditory, and, as learning progresses, they evolve from a broadly tuned initial state to a state of strong preference for the bird's own song and acute sensitivity to the temporal order of this song. Moreover, normal synaptic activity in LMAN is required during sensory learning for accurate tutor song copying to occur (). To explore cellular and synaptic properties of LMAN that may contribute to this crucial stage of song acquisition, we developed an acute slice preparation of LMAN from zebra finches in the early stages of sensory learning (18-25 days posthatch). We used this preparation to examine intrinsic neuronal properties of LMAN neurons at this stage and to identify two independent excitatory inputs to these neurons and compare each input's pharmacology and short-term synaptic plasticity. LMAN neurons had immature passive membrane properties, well-developed spiking behavior, and received excitatory input from two sources: afferents from the medial portion of the dorsolateral thalamus (DLM), and recurrent axon collaterals from LMAN itself ("intrinsic" input). These two inputs differed in both their pharmacology and temporal properties. Both inputs were glutamatergic, but LMAN responses to intrinsic inputs exhibited a larger N-methyl--aspartate component than responses to DLM inputs. Both inputs elicited temporal summation in response to pairs of stimuli delivered at short intervals, but -2-amino-5-phosphonovalerate (APV) significantly reduced the temporal summation only of the responses to intrinsic inputs. Moreover, responses to DLM inputs showed consistent paired-pulse depression, whereas the responses to intrinsic inputs did not. The differences between these two inputs suggest that intrinsic circuitry plays an important role in transforming DLM input patterns into the appropriate LMAN output patterns, as has been suggested for mammalian thalamocortical networks. Moreover, in LMAN, such interactions may contribute to the profound temporal and spectral selectivity that these neurons will acquire during learning.     

A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity

The current view of the role of GABAergic interneurones in cortical-network function has shifted from one of merely dampening neuronal activity to that of an active role in information processing. In this review, we explore a potential role of hippocampal GABAergic interneurones in providing spatial and temporal conditions for modifications of synaptic weights during hippocampus-dependent memory processes. We argue that knowledge of spatiotemporal activity patterns in distinct classes of interneurone is essential to understanding the cellular mechanisms underlying learning and memory.     

Noradrenergic suppression of synaptic transmission may influence cortical signal-to-noise ratio

Norepinephrine has been proposed to influence signal-to-noise ratio within cortical structures, but the exact cellular mechanisms underlying this influence have not been described in detail. Here we present data on a cellular effect of norepinephrine that could contribute to the influence on signal-to-noise ratio. In brain slice preparations of the rat piriform (olfactory) cortex, perfusion of norepinephrine causes a dose-dependent suppression of excitatory synaptic potentials in the layer containing synapses among pyramidal cells in the cortex (layer Ib), while having a weaker effect on synaptic potentials in the afferent fiber layer (layer Ia). Effects of norepinephrine were similar in dose-response characteristics and laminar selectivity to the effects of the cholinergic agonist carbachol, and combined perfusion of both agonists caused effects similar to an equivalent concentration of a single agonist. In a computational model of the piriform cortex, we have analyzed the effect of noradrenergic suppression of synaptic transmission on signal-to-noise ratio. The selective suppression of excitatory intrinsic connectivity decreases the background activity of modeled neurons relative to the activity of neurons receiving direct afferent input. This can be interpreted as an increase in signal-to-noise ratio, but the term noise does not accurately characterize activity dependent on the intrinsic spread of excitation, which would more accurately be described as interpretation or retrieval. Increases in levels of norepinephrine mediated by locus coeruleus activity appear to enhance the influence of extrinsic input on cortical representations, allowing a pulse of norepinephrine in an arousing context to mediate formation of memories with a strong influence of environmental variables.     

Self and informant ratings of SCID-II Personality Disorder items for nonreferred college women: effects of item and participant characteristics

Tufted layer 5 (TL5) pyramidal neurons are important projection neurons from the cerebral cortex to subcortical areas. Recent and ongoing experiments aimed at understanding the computational analysis performed by a network of synaptically connected TL5 neurons are reviewed here. The experiments employed dual and triple whole-cell patch clamp recordings from visually identified and preselected neurons in brain slices of somatosensory cortex of young (14- to 16-day-old) rats. These studies suggest that a local network of TL5 neurons within a cortical module of diameter 300 microns consists of a few hundred neurons that are extensively inter-connected with reciprocal feedback from at least first-, second- and third-order target neurons. A statistical analysis of synaptic innervation suggests that this recurrent network is not randomly arranged and hence each neuron could be functionally unique. Synaptic transmission between these neurons is characterized by use-dependent synaptic depression which confers novel properties to this recurrent network of neurons. First, a range of rates of depression for different synaptic connections enable each TL5 neuron to receive a unique mixture of information about the average firing rates and the temporally correlated action potential (AP) activity in the population of presynaptic TL5 neurons. Second, each AP generated by any neuron in the network induces a change (defined as an iteration step) in the functional coupling of the neurons in the network (defined as network configuration). It is proposed that the network configuration is iterated during a stimulus to achieve an optimally orchestrated network response. Hebbian, anti-Hebbian and neuromodulatory-induced modifications of neurotransmitter release probability change the rates of synaptic depression and thereby alter the iteration step size. These data may be important to understand the dynamics of electrical activity within the network.     

Synchronization of neuronal activity promotes survival of individual rat neocortical neurons in early development

Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.     

Global precedence in visual search? Not so fast: evidence instead for an oblique effect

We used the dual-task paradigm to provide evidence that inferring the motion of a component of a mechanical system (mental animation) is a spatial visualization process. In two experiments, participants were asked to solve mental animation problems while simultaneously retaining either a visuospatial working memory load (a configuration of dots in a grid) or a verbal memory load (a list of letters). Both experiments showed that mental animation interferes more with memory for a concurrent visuospatial load than with memory for a verbal load. Experiment 1 also showed that a visuospatial working memory load interferes more with mental animation than does a verbal memory load. Furthermore, Experiment 2 showed that mental animation interferes more with a visuospatial memory load than does a verbal reasoning task that takes approximately the same amount of time.     

Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons

Activity-dependent modification of synaptic efficacy is widely recognized as a cellular basis of learning, memory, and developmental plasticity. Little is known, however, of the consequences of such modification on network activity. Using electrode arrays, we examined how a single, localized tetanic stimulus affects the firing of up to 72 neurons recorded simultaneously in cultured networks of cortical neurons, in response to activation through 64 different test stimulus pathways. The same tetanus produced potentiated transmission in some stimulus pathways and depressed transmission in others. Unexpectedly, responses were homogeneous: for any one stimulus pathway, neuronal responses were either all enhanced or all depressed. Cross-correlation of responses with the responses elicited through the tetanized site revealed that both enhanced and depressed responses followed a common principle: activity that was closely correlated before tetanus with spikes elicited through the tetanized pathway was enhanced, whereas activity outside a 40-ms time window of correlation to tetanic pathway spikes was depressed. Response homogeneity could result from pathway-specific recurrently excitatory circuits, whose gain is increased or decreased by the tetanus, according to its cross-correlation with the tetanized pathway response. The results show how spatial responses following localized tetanic stimuli, although complex, can be accounted for by a simple rule for activity-dependent modification.     

In vivo induction of the interferon-stimulated protein 2''5''-oligoadenylate synthetase in tumor and peripheral blood cells during IFN-alpha treatment of metastatic melanoma

Learning, making memories, and forgetting are thought to require changes in the strengths of connections between neurons. Such changes in synaptic strength occur in two phases: an early phase that is likely mediated by covalent modifications to existing proteins, and a delayed phase that depends on new gene expression and protein synthesis. However, the biochemical mechanisms by which neuronal activity leads to changes in synaptic strength are poorly understood. Recently, it has been shown that animals that lack Ras guanine nucleotide releasing factor (Ras-GRF), a Ca(2+)-dependent activator of the small GTP-binding protein, Ras, do not learn fear responses normally, although other types of learning appear normal. These animals show defects in the delayed phase of memory formation within the neuronal circuit that mediates fear conditioning. This paper suggests that Ras-GRF couples synaptic activity to the molecular mechanisms that consolidate changes in synaptic strength within specific neuronal circuits.     

Green fluorescent protein expressed by a recombinant vaccinia virus permits early detection of infected cells by flow cytometry

One of the most prominent effects of Alzheimer disease is the disruption of finely tuned neuronal circuitry of discrete brain regions associated with learning and memory. Results from the present study support a role for the intrinsic inhibitory component of neuronal circuitry in determining the magnitude of beta-amyloid peptide induced cell death in the highly vulnerable pyramidal neurons of the hippocampus. Previous efforts have mostly focused on direct effects on excitatory neurons. By contrast, less emphasis has been placed on addressing a role for the intrinsic inhibitory component of cell-cell interactions of neuronal networks in response to Abeta. The present study provides evidence demonstrating that blockage of the intrinsic inhibitory component between Abeta exposed neurons leads to destabilization of calcium homeostasis and exacerbated neuronal death compared to Abeta treated cultures. Neuronal electrical activity was first silenced by exposing cultures to tetrodotoxin (TTX; 100 nM) plus Abeta, followed by survival counts. Cell death, unexpectedly, did not significantly differ from Abeta-exposed neurons. The intrinsic inhibition in Abeta-exposed cultures was then pharmacologically removed with picrotoxin (40 microM) or bicuculline (25 microM) resulting in significantly greater death than Abeta-exposed neurons alone. From these observations, it is proposed that intrinsic functional inhibition in hippocampal circuits can reduce adverse effects of Abeta on the excitatory component. By considering not just the excitatory component of electrical activity, but the intrinsic balance between excitation and inhibition, new strategies for the treatment of Alzheimer disease may emerge.     

Neural correlates of directed forgetting in the avian prefrontal cortex.

The authors trained 2 homing pigeons (Columba livia) on a directed forgetting task with 3 cues: a remember cue that was followed by a memory test and the opportunity to obtain a reward, a forget cue that was not followed by a memory test or a reward, and a free-reward cue that was not followed by a memory test but was followed by a free reward. The authors examined the activity of single neurons in the avian nidopallium caudolaterale, an area equivalent to the primate prefrontal cortex. Following the remember cue there was sustained neural activity during the delay period, whereas following the forget cue the neural activity in the delay period was significantly reduced. The activity following the free-reward cue mirrored that following the remember cue. The authors discuss the extent to which the findings are in line with the view that the sustained activity reflects memory for the sample stimulus or memory for reward. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Targeted gene misexpression in chick limb buds using avian replication-competent retroviruses

We analyze the control of frequency for a synchronized inhibitory neuronal network. The analysis is done for a reduced membrane model with a biophysically based synaptic influence. We argue that such a reduced model can quantitatively capture the frequency behavior of a larger class of neuronal models. We show that in different parameter regimes, the network frequency depends in different ways on the intrinsic and synaptic time constants. Only in one portion of the parameter space, called phasic, is the network period proportional to the synaptic decay time. These results are discussed in connection with previous work of the authors, which showed that for mildly heterogeneous networks, the synchrony breaks down, but coherence is preserved much more for systems in the phasic regime than in the other regimes. These results imply that for mildly heterogeneous networks, the existence of a coherent rhythm implies a linear dependence of the network period on synaptic decay time and a much weaker dependence on the drive to the cells. We give experimental evidence for this conclusion.