Output Station Research Articles

Increased GABAergic Efficacy of Central Amygdala Projections to Neuropeptide S Neurons in the Brainstem During Fear Memory Retrieval.

The canonical view on the central amygdala has evolved from a simple output station towards a highly organized microcircuitry, in which types of GABAergic neurons in centrolateral (CeL) and centromedial (CeM) subnuclei regulate fear expression and generalization. How these specific neuronal populations are connected to extra-amygdaloid target regions remains largely unknown. Here we show in mice that a subpopulation of GABAergic CeL and CeM neurons projects monosynaptically to brainstem neurons expressing neuropeptide S (NPS). The CeL neurons are PKCδ-negative and are activated during conditioned fear. During fear memory retrieval, the efficacy of this GABAergic influence on NPS neurons is enhanced. Moreover, a large proportion of these neurons (~50%) contain prodynorphin and somatostatin, two neuropeptides inhibiting NPS neurons. We conclude that CeL and CeM neurons inhibit NPS neurons in the brainstem by GABA release and that efficacy of this connection is strengthened upon fear memory retrieval. Thereby, this pathway provides a possible feedback mechanism between amygdala and brainstem routes involved in fear and stress coping.

Extracting Information: Characterizing neuronal cell types in the GPh by their activity profile.

The globus pallidus is a major output station for the basal ganglia, a subcortical region of the brain that is heavilyimplicated in action selection and decision making. A subpopulation of neurons in the internal segment (GPi) projects tothe laternal habenula (LHb), often associated with the limbic system and known to encode for negative motivational value.Dysfunction in these structures have been implicated in neurological diseases, such as depression and schizophrenia,which are ultimately disruptions in the ability to evaluate environmental cues and regulate motor output. In order togain more information about the neurons which encode for this behavior, we conducted extracellular recordings whilethe mice are carrying out a set of reward learning tasks and analyzed the collected spike trains. We detail here themethods of information extraction from the neuronal populations that we have classified. We also present preliminaryresults of their activity profile for various outcomes as well as for reward history and prediction error. With collection ofinformation from a larger set of cells, we might be able to more definitively gain an understanding of the methods bywhich these neurons encode motivation, action selection and outcome evaluation.

A Role for Tac2, NkB, and Nk3 Receptor in Normal and Dysregulated Fear Memory Consolidation

The centromedial amygdala (CeM), a subdivision of the central amygdala (CeA), is believed to be the main output station of the amygdala for fear expression. We provide evidence that the Tac2 gene, expressed by neurons specifically within the CeM, is required for modulating fear memories. Tac2 is colocalized with GAD65 and CaMKIIα but not with PKCd and Enk neurons in the CeM. Moreover, the Tac2 product, NkB, and its specific receptor, Nk3R, are also involved in the consolidation of fear memories. Increased Tac2 expression, through a stress-induced PTSD-like model, or following lentiviral CeA overexpression, are sufficient to enhance fear consolidation. This effect is blocked by the Nk3R antagonist osanetant. Concordantly, silencing of Tac2-expressing neurons in CeA with DREADDs impairs fear consolidation. Together, these studies further our understanding of the role of the Tac2 gene and CeM in fear processing and may provide approaches to intervention for fear-related disorders.

Spatial mapping of pan evaporation using linear genetic programming

Daily pan evaporation is of utmost importance in planning and managing water resources. The present paper involves estimation of daily pan evaporation at a particular climatic station using daily pan evaporations of surrounding ten climatic stations covering six districts of Maharashtra state (India) with variation in elevations and weather. The surrounding stations were added one by one based on the correlation of each station with the output station. The soft computing technique of linear genetic programming was employed for this spatial mapping exercise. The models were developed for each station as output station (total 11) with the remaining stations (1 to 10) as inputs added one by one. In all 110 LGP models were developed to examine the ability of linear genetic programming to work as virtual pan as and when existing evaporimeters become inoperative. The best LGP model was for Suksale station with coefficient of correlation (r = 0.94) between observed and estimated pan evaporation. This will retrieve the missing evaporation data at one location using data at other locations.

Nowcasting with INCA During SNOW-V10

A Central-European nowcasting system which has been developed for use in mountainous terrain is tested in the Whistler/Vancouver area as part of the SNOW-V10 experiment. The integrated nowcasting through comprehensive analysis system provides hourly updated gridded forecasts of temperature, humidity, and wind, as well as precipitation forecasts which are updated every 15 min. It is based on numerical weather prediction (NWP) output and real-time surface weather station and radar data. Verification of temperature, relative humidity, and wind against surface stations shows that forecast errors are significantly reduced in the nowcasting range compared to those of the driving NWP model. The main contribution to the improvement comes from the implicit bias correction due to use of the latest observations. Relative humidity shows the longest lasting effect, with >50 % reduction of mean absolute error up to +4 h. For temperature and wind speed this percentage is reached after +2 and +3 h, respectively. Two cases of precipitation nowcasting are discussed and verified qualitatively.

Overview: asset management – gas turbine power stations

This overview was written primarily with graduates, engineers and electrical, mechanical, chemical, instrumentation and control and computer technicians in mind who wish to enter the power generation industry at large and gas turbine power generating plants in particular, since combined cycle gas turbine power plants constitute the largest output and most efficient turbine power generation stations operating today. This Part 3 of a four part overview focuses on the salient asset management aspects of combined cycle steam turbine/generator–exciter units.

Affective Neuroscience: Tracing the Trace of Fear

The trace of fear has been elusive and difficult to discern in the human brain. Researchers have come up with a clever new way to track it down.

Layer dependent neural modulation of a realistic layered-microcircuit model in visual cortex based on bottom-up and top-down signals

Visual attention allocates the information processing resources of the brain to selected sensory inputs to reduce the processing load. Here, we carried out a large-scale simulation with a layered-microcircuit model of the visual cortex based on current knowledge of cortical neurobiology to explore the complex interaction between bottom-up visual input and top-down attentional signals. The microcircuit model corresponds to two columns of visual cortex. Each column consists of about 40,000 integrate-and-fire neurons comprising layers 2/3, 4, 5 and 6 [1]. These columns interact via lateral inhibition from layer 2/3 excitatory neurons in one column to layer 2/3 inhibitory neurons in the other, so that the full network comprises in total around 80,000 neurons and 300 million synapses. Excitatory and inhibitory neurons in layer 4 of the model receive visual inputs mimicking vertical and horizontal bars. Top-down attention was projected to layers 2/3 and 5 to facilitate the visual processing. In order to investigate the mechanism of visual processing and the attentional effect in the layered-microcircuit model, we compared the response of the model to physiological results for neural and attentional modulation [2]. Our model successfully reproduced previous experimental observations of stimulus presentation and attentional effects on visual neuronal responses in layers 2/3 and 5 (Figure ​(Figure1).1). Moreover, the model predicts contrasting differences in the effects of attention between cortical layers: attention to a preferred stimulus of a column enhances neuronal responses of layers 2/3 and 5, the output station of cortical microcircuits, whereas attention suppresses neuronal activities of layer 4, the input station of cortical microcircuits. Further simulations with our model suggest that the specific attentional modulation pattern of layer 4 activity emerges from inter-laminar synaptic connections within the cortical microcircuit and is crucial for the microcircuit to rapidly shift attention to a stimulus different from the one currently attended to. Our multicolumnar model is a canonical microcircuit model for the dynamic selection of multiple sensory inputs to the visual cortices, and makes several testable predictions about the layer-dependence of the response modulations. Figure 1 The population firing rates of excitatory (filled bars) and inhibitory (empty bars) neurons are shown for each layer of a column for various combinations of visual and attentional inputs. The preferred stimulus of the column is bordered white. An attended ...

Impact of infralimbic inputs on intercalated amygdala neurons: A biophysical modeling study

Intercalated (ITC) amygdala neurons regulate fear expression by controlling impulse traffic between the input (basolateral amygdala; BLA) and output (central nucleus; Ce) stations of the amygdala for conditioned fear responses. Previously, stimulation of the infralimbic (IL) cortex was found to reduce fear expression and the responsiveness of Ce neurons to BLA inputs. These effects were hypothesized to result from the activation of ITC cells projecting to Ce. However, ITC cells inhibit each other, leading to the question of how IL inputs could overcome the inter-ITC inhibition to regulate the responses of Ce neurons to aversive conditioned stimuli (CSs). To investigate this, we first developed a compartmental model of a single ITC cell that could reproduce their bistable electroresponsive properties, as observed experimentally. Next, we generated an ITC network that implemented the experimentally observed short-term synaptic plasticity of inhibitory inter-ITC connections. Model experiments showed that strongly adaptive CS-related BLA inputs elicited persistent responses in ITC cells despite the presence of inhibitory interconnections. The sustained CS-evoked activity of ITC cells resulted from an unusual slowly deinactivating K(+) current. Finally, over a wide range of stimulation strengths, brief IL activation caused a marked increase in the firing rate of ITC neurons, leading to a persistent decrease in Ce output, despite inter-ITC inhibition. Simulations revealed that this effect depended on the bistable properties and synaptic heterogeneity of ITC neurons. These results support the notion that IL inputs are in a strategic position to control extinction of conditioned fear via the activation of ITC neurons.

Central Amygdala Activity during Fear Conditioning

The central amygdala (Ce), particularly its medial sector (CeM), is the main output station of the amygdala for conditioned fear responses. However, there is uncertainty regarding the nature of CeM control over conditioned fear. The present study aimed to clarify this question using unit recordings in rats. Fear conditioning caused most CeM neurons to increase their conditioned stimulus (CS) responsiveness. The next day, CeM cells responded similarly during the recall test, but these responses disappeared as extinction of conditioned fear progressed. In contrast, the CS elicited no significant average change in central lateral (CeL) firing rates during fear conditioning and a small but significant reduction during the recall test. Yet, cell-by-cell analyses disclosed large but heterogeneous CS-evoked responses in CeL. By the end of fear conditioning, roughly equal proportions of CeL cells exhibited excitatory (CeL(+)) or inhibitory (CeL(-)) CS-evoked responses (∼10%). The next day, the proportion of CeL(-) cells tripled with no change in the incidence of CeL(+) cells, suggesting that conditioning leads to overnight synaptic plasticity in an inhibitory input to CeL(-) cells. As in CeM, extinction training caused the disappearance of CS-evoked activity in CeL. Overall, these findings suggest that conditioned freezing depends on increased CeM responses to the CS. The large increase in the incidence of CeL(-) but not CeL(+) cells from conditioning to recall leads us to propose a model of fear conditioning involving the potentiation of an extrinsic inhibitory input (from the amygdala or elsewhere) to CeL, ultimately leading to disinhibition of CeM neurons.

Filling of missing rainfall data in Luvuvhu River Catchment using artificial neural networks

Incomplete data with gaps is always a challenge in hydrological modeling and water resources planning and management. Complete and reliable data is required for water resources planning and management. A study was done in the Luvuvhu River Catchment (LRC) with the aim of filling missing rainfall data. This was done with the aid of artificial neural networks (ANNs) using a radial basis function. The Root Mean Square Error (RMSE) was used as an objective function in the calibration phase. The Shuffled Complex Evolution (SCE) was used to find optimal parameters of the ANNs. Reliable rainfall data from surrounding stations was used as inputs to fill in missing rainfall data for an output station. A double mass curve was plotted to check the quality of rainfall data of the output station against the surrounding stations. Not all the stations in the LRC showed good correlation. However, data selected for training and testing from all the patched stations performed well. The measures of model performance fell within the acceptable ranges in hydrological modeling for all stations. During the calibration phase the Nash–Sutcliffe Efficiency (NSE) ranged from 0.55 to 0.85 and the percent bias ranged from −2% to 23%. In the validation process NSE range was between 0.49 and 0.75 and percent bias was between 2% and 19%. The values of NSE and percent bias were satisfactory to good, and acceptable respectively. This study has shown that ANNs are suitable for estimating missing rainfall data in the LRC. The study has produced reliable rainfall data that can be used in hydrological modeling and water resources planning and management.

Layer-Dependent Attentional Processing by Top-down Signals in a Visual Cortical Microcircuit Model

A vast amount of information about the external world continuously flows into the brain, whereas its capacity to process such information is limited. Attention enables the brain to allocate its resources of information processing to selected sensory inputs for reducing its computational load, and effects of attention have been extensively studied in visual information processing. However, how the microcircuit of the visual cortex processes attentional information from higher areas remains largely unknown. Here, we explore the complex interactions between visual inputs and an attentional signal in a computational model of the visual cortical microcircuit. Our model not only successfully accounts for previous experimental observations of attentional effects on visual neuronal responses, but also predicts contrasting differences in the attentional effects of top-down signals between cortical layers: attention to a preferred stimulus of a column enhances neuronal responses of layers 2/3 and 5, the output stations of cortical microcircuits, whereas attention suppresses neuronal responses of layer 4, the input station of cortical microcircuits. We demonstrate that the specific modulation pattern of layer-4 activity, which emerges from inter-laminar synaptic connections, is crucial for a rapid shift of attention to a currently unattended stimulus. Our results suggest that top-down signals act differently on different layers of the cortical microcircuit.

Central, but not basolateral, amygdala involvement in the anxiolytic-like effects of midazolam in rats in the elevated plus maze

The role of the amygdala in the mediation of fear and anxiety has been extensively investigated. However, how the amygdala functions during the organization of the anxiety-like behaviors generated in the elevated plus maze (EPM) is still under investigation. The basolateral (BLA) and the central (CeA) nuclei are the main input and output stations of the amygdala. In the present study, we ethopharmacologically analyzed the behavior of rats subjected to the EPM and the tissue content of the monoamines dopamine (DA) and serotonin (5-HT) and their metabolites in the nucleus accumbens (NAc), dorsal hippocampus (DH), and dorsal striatum (DS) of animals injected with saline or midazolam (20 and 30 nmol/0.2 µL) into the BLA or CeA. Injections of midazolam into the CeA, but not BLA, caused clear anxiolytic-like effects in the EPM. These treatments did not cause significant changes in 5-HT or DA contents in the NAc, DH, or DS of animals tested in the EPM. The data suggest that the anxiolytic-like effects of midazolam in the EPM also appear to rely on GABA-benzodiazepine mechanisms in the CeA, but not BLA, and do not appear to depend on 5-HT and DA mechanisms prevalent in limbic structures.

Origins of multisynaptic projections from the basal ganglia to rostrocaudally distinct sectors of the dorsal premotor area in macaques

We examined the organization of multisynaptic projections from the basal ganglia (BG) to the dorsal premotor area in macaques. After injection of the rabies virus into the rostral sector of the caudal aspect of the dorsal premotor area (F2r) and the caudal sector of the caudal aspect of the dorsal premotor area (F2c), second-order neuron labeling occurred in the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr). Labeled GPi neurons were found in the caudoventral portion after F2c injection, and in the dorsal portion at the rostrocaudal middle level after F2r injection. In the SNr, F2c and F2r injections led to labeling in the caudal or rostral part, respectively. Subsequently, third-order neuron labeling was observed in the external segment of the globus pallidus (GPe), the subthalamic nucleus (STN), and the striatum. After F2c injection, labeled neurons were observed over a broad territory in the GPe, whereas after F2r injection, labeled neurons tended to be restricted to the rostral and dorsal portions. In the STN, F2c injection resulted in extensive labeling over the nucleus, whereas F2r injection resulted in labeling in the ventral portion only. After both F2r and F2c injections, labeled neurons in the striatum were widely observed in the striatal cell bridge region and neighboring areas, as well as in the ventral striatum. The present results revealed that the origins of multisynaptic projections to F2c and F2r in the BG are segregated in the output stations of the BG, whereas intermingling rather than segregation is evident with respect to their input station.

Differential role of GABA A and GABA B receptors in two distinct output stations of the rat striatum: studies on the substantia nigra pars reticulata and the globus pallidus

The role of GABA A and GABA B receptors in the substantia nigra pars reticulata and the globus pallidus in turning behaviour of rats was studied. Unilateral injection of the GABA A receptor agonist muscimol (25 and 50 ng) into the substantia nigra pars reticulata elicited contralateral pivoting, namely tight head-to-tail turning marked by abnormal hindlimb backward stepping. This effect was GABA A receptor specific, since it was dose-dependent and prevented by co-administration of the GABA A receptor antagonist bicuculline (100 and 200 ng) which alone did not elicit turning behaviour. Unilateral injection of the GABA B receptor agonist baclofen (100 and 200 ng) into the substantia nigra pars reticulata also produced contralateral pivoting. This effect was GABA B receptor specific, since it was dose-dependent and inhibited by the GABA B receptor antagonist CGP 55845 (200 ng) which alone did not elicit turning behaviour. In contrast, unilateral injection of bicuculline (100 and 200 ng) into the globus pallidus produced contralateral circling, namely turning marked by normal stepping. This effect was GABA A receptor specific, since it was dose-dependent and prevented by muscimol (50 ng), which alone did not elicit turning behaviour. Unilateral injection of baclofen (100 and 200 ng) into the globus pallidus dose-dependently produced ipsilateral pivoting; this effect was inhibited by CGP 55845 (200 ng), which alone did not elicit turning behaviour. The present study demonstrates that GABA A and GABA B receptors in the globus pallidus and the substantina nigra pars reticulata play differential roles in the production of turning behaviour. This study underlines the notion that the two types of turning, namely pivoting and circling, are valid tools to map out the information flow across the basal ganglia.

Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson's disease

The thalamic centre median-parafascicular complex (CM/Pf), a main input and output station of the basal ganglia, is attracting increasing interest in the field of movement disorders, including Parkinson's disease (PD). CM/Pf undergoes partial neurodegeneration in PD patients and some rodent models. Cellular evidence has been provided in experimental animals that thalamic degeneration may not aggravate but rather counteract the effects of dopamine lesion. But functional changes in the circuits involving the spared neurons could play a detrimental role. This view fits with converging anecdotic and recent direct experience in patients that stress the potential of CM/PF deep brain stimulation (DBS) to alleviate motor disorders, notably tremor and dyskinesias. As a preclinical contribution to the characterization of this target, we investigated the functional impact of CM/Pf-DBS in the 6-hydroxydopamine hemiparkinsonian rat model of PD. When testing different frequencies (25, 60, 130 Hz), only high frequency stimulation (HFS) had significant antiakinetic action as evidenced by alleviation of limb use asymmetry in the cylinder test. Although less efficient than HFS of the subthalamic nucleus in the latter task, CM/PF-HFS completely corrected lateralized neglect in the corridor task. Unlike subthalamic nucleus, CM/Pf-HFS did not induce per se dyskinesias. Finally, the benefits provided by CM/Pf-HFS were associated with widespread impact on the changes in neuronal metabolic activity induced by the dopamine depletion in the basal ganglia. These data point to own particular outcome of CM/Pf-DBS that may be of interest in currently developing multi-target strategies.

The Globus Pallidus Sends Reward-Related Signals to the Lateral Habenula

As a major output station of the basal ganglia, the globus pallidus internal segment (GPi) projects to the thalamus and brainstem nuclei thereby controlling motor behavior. A less well known fact is that the GPi also projects to the lateral habenula (LHb) which is often associated with the limbic system. Using the monkey performing a saccade task with positionally biased reward outcomes, we found that antidromically identified LHb-projecting neurons were distributed mainly in the dorsal and ventral borders of the GPi and that their activity was strongly modulated by expected reward outcomes. A majority of them were excited by the no-reward-predicting target and inhibited by the reward-predicting target. These reward-dependent modulations were similar to those in LHb neurons but started earlier than those in LHb neurons. These results suggest that GPi may initiate reward-related signals through its effects on the LHb, which then influences the dopaminergic and serotonergic systems.

Amygdala intercalated neurons are required for expression of fear extinction

Congruent findings from studies of fear learning in animals and humans indicate that research on the circuits mediating fear constitutes our best hope of understanding human anxiety disorders. In mammals, repeated presentations of a conditioned stimulus that was previously paired to a noxious stimulus leads to the gradual disappearance of conditioned fear responses. Although much evidence suggests that this extinction process depends on plastic events in the amygdala, the underlying mechanisms remain unclear. Intercalated (ITC) amygdala neurons constitute probable mediators of extinction because they receive information about the conditioned stimulus from the basolateral amygdala (BLA), and contribute inhibitory projections to the central nucleus (CEA), the main output station of the amygdala for conditioned fear responses. Thus, after extinction training, ITC cells could reduce the impact of conditioned-stimulus-related BLA inputs to the CEA by means of feed-forward inhibition. Here we test the hypothesis that ITC neurons mediate extinction by lesioning them with a toxin that selectively targets cells expressing micro-opioid receptors (microORs). Electron microscopic observations revealed that the incidence of microOR-immunoreactive synapses is much higher in ITC cell clusters than in the BLA or CEA and that microORs typically have a post-synaptic location in ITC cells. In keeping with this, bilateral infusions of the microOR agonist dermorphin conjugated to the toxin saporin in the vicinity of ITC neurons caused a 34% reduction in the number of ITC cells but no significant cell loss in surrounding nuclei. Moreover, ITC lesions caused a marked deficit in the expression of extinction that correlated negatively with the number of surviving ITC neurons but not CEA cells. Because ITC cells exhibit an unusual pattern of receptor expression, these findings open new avenues for the treatment of anxiety disorders.

Evaluation of an Automated Instrument for Inoculating and Spreading Samples onto Agar Plates

The findings from a preliminary assessment of a new instrument designed for the inoculation and spreading of specimens for microbiological analysis onto agar plates are described. The study found that the instrument was able to select full or biplates from a number of input cassettes, each containing different agar types. Samples were then inoculated by the instrument onto the agar surfaces and spread by a novel plastic applicator. Following this, the instrument labeled the plates and sorted them into a number of specified output stations. It was found that the instrument was able to inoculate and spread samples over a greater proportion of the agar plate surface than the manual loop-to-plate method. As a consequence, up to 44% more usable colonies were produced per plate from clinical specimens and standard cultures. Viable counts showed that the instrument was able to detect as few as 10(2) CFU/ml in fluids and also facilitated the enumeration of organisms, particularly in specimens such as urine.

Functional Responses in the Human Spinal Cord during Willed Motor Actions: Evidence for Side- and Rate-Dependent Activity

Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functional activity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magnetic resonance imaging (fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handed volunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace (approximately 0.5 Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the side of the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signal fluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed using the dominant hand at two different rates (approximately 0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higher rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique, the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin and that as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on the activity of spinal circuits.