scholarly journals Dopamine-Mediated Stabilization of Delay-Period Activity in a Network Model of Prefrontal Cortex

2000 ◽  
Vol 83 (3) ◽  
pp. 1733-1750 ◽  
Author(s):  
Daniel Durstewitz ◽  
Jeremy K. Seamans ◽  
Terrence J. Sejnowski
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Network Model ◽  
Delay Period ◽  
D1 Receptor ◽  
Neural Representations ◽  
Type Activity ◽  
Synaptic Conductances

The prefrontal cortex (PFC) is critically involved in working memory, which underlies memory-guided, goal-directed behavior. During working-memory tasks, PFC neurons exhibit sustained elevated activity, which may reflect the active holding of goal-related information or the preparation of forthcoming actions. Dopamine via the D1 receptor strongly modulates both this sustained (delay-period) activity and behavioral performance in working-memory tasks. However, the function of dopamine during delay-period activity and the underlying neural mechanisms are only poorly understood. Recently we proposed that dopamine might stabilize active neural representations in PFC circuits during tasks involving working memory and render them robust against interfering stimuli and noise. To further test this idea and to examine the dopamine-modulated ionic currents that could give rise to increased stability of neural representations, we developed a network model of the PFC consisting of multicompartment neurons equipped with Hodgkin-Huxley-like channel kinetics that could reproduce in vitro whole cell and in vivo recordings from PFC neurons. Dopaminergic effects on intrinsic ionic and synaptic conductances were implemented in the model based on in vitro data. Simulated dopamine strongly enhanced high, delay-type activity but not low, spontaneous activity in the model network. Furthermore the strength of an afferent stimulation needed to disrupt delay-type activity increased with the magnitude of the dopamine-induced shifts in network parameters, making the currently active representation much more stable. Stability could be increased by dopamine-induced enhancements of the persistent Na+and N-methyl-d-aspartate (NMDA) conductances. Stability also was enhanced by a reductionin AMPA conductances. The increase in GABAA conductances that occurs after stimulation of dopaminergic D1 receptors was necessary in this context to prevent uncontrolled, spontaneous switches into high-activity states (i.e., spontaneous activation of task-irrelevant representations). In conclusion, the dopamine-induced changes in the biophysical properties of intrinsic ionic and synaptic conductances conjointly acted to highly increase stability of activated representations in PFC networks and at the same time retain control over network behavior and thus preserve its ability to adequately respond to task-related stimuli. Predictions of the model can be tested in vivo by locally applying specific D1 receptor, NMDA, or GABAA antagonists while recording from PFC neurons in delayed reaction-type tasks with interfering stimuli.

CONTRIBUTION TO THE EXISTENCE OF REGULATORY MECHANISMS AT THE ADRENAL LEVEL

1972 ◽  
Vol 70 (4) ◽  
pp. 741-757
Author(s):  
Otto Linèt
Keyword(s):  
Orotic Acid ◽  
Adrenal Glands ◽  
Actinomycin D ◽  
Delay Period ◽  
Regulatory Mechanisms ◽  
Leucine Incorporation ◽  
Total Period ◽  
Free Media

ABSTRACT Rat adrenal glands atrophied by the administration of cortisol acetate in vivo were used as a model for the study of early metabolic processes occurring in vitro. Atrophied adrenals incubated in the presence of 14C-leucine incorporated subnormal quantities of this amino acid per mg of protein for the first 120 min. When the incubation lasted for a total period of 180 or 240 min a supranormal rise in the 14C-leucine incorporation was observed. Similar changes occurred with some delay with regard to corticosterone production as expressed per 100 mg of tissue. No differences in 14C-leucine incorporation were observed between the control and atrophied adrenals in vivo. Homogenates from atrophied glands incorporated 14C-leucine to a greater extent than the control homogenates. The in vitro incorporation of 14C-orotic acid into the RNA was also higher in atrophied adrenals. The in vitro use of actinomycin D, cycloheximide and amphenone indicated that corticosterone production depended on the incorporation of 14C-leucine. The addition of cortisol to the incubation media markedly decreased the enhancement of 14C-lysine incorporation into the protein of atrophied adrenals. These, as well as additional results suggest rebound phenomena: once atrophic adrenals are transferred to cortisol-free media, reparative processes begin after a delay period. Such phenomena seem to be mediated by regulatory mechanisms at the adrenal level.

scholarly journals A Method to Estimate Synaptic Conductances From Membrane Potential Fluctuations

2004 ◽  
Vol 91 (6) ◽  
pp. 2884-2896 ◽  
Author(s):  
Michael Rudolph ◽  
Zuzanna Piwkowska ◽  
Mathilde Badoual ◽  
Thierry Bal ◽  
Alain Destexhe
Keyword(s):  
Membrane Potential ◽  
Computational Models ◽  
Network Activity ◽  
Intracellular Recordings ◽  
Neocortical Neurons ◽  
Underlying Network ◽  
Analytic Expression ◽  
Synaptic Conductances

In neocortical neurons, network activity can activate a large number of synaptic inputs, resulting in highly irregular subthreshold membrane potential ( Vm) fluctuations, commonly called “synaptic noise.” This activity contains information about the underlying network dynamics, but it is not easy to extract network properties from such complex and irregular activity. Here, we propose a method to estimate properties of network activity from intracellular recordings and test this method using theoretical and experimental approaches. The method is based on the analytic expression of the subthreshold Vm distribution at steady state in conductance-based models. Fitting this analytic expression to Vm distributions obtained from intracellular recordings provides estimates of the mean and variance of excitatory and inhibitory conductances. We test the accuracy of these estimates against computational models of increasing complexity. We also test the method using dynamic-clamp recordings of neocortical neurons in vitro. By using an on-line analysis procedure, we show that the measured conductances from spontaneous network activity can be used to re-create artificial states equivalent to real network activity. This approach should be applicable to intracellular recordings during different network states in vivo, providing a characterization of the global properties of synaptic conductances and possible insight into the underlying network mechanisms.

scholarly journals Delay-Period Activity and Executive Functions of the Prefrontal Cortex

2019 ◽  
Vol 10 (1) ◽  
pp. 3
Author(s):  
Aarron Phensy ◽  
Sven Kroener
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Executive Functions ◽  
Delay Period ◽  
Goal Directed Behavior

The term “working memory” (WM) describes the ability to maintain and manipulate information in the memory for the guidance of goal-directed behavior [...]

Cellular and Network Mechanisms of Slow Oscillatory Activity (<1 Hz) and Wave Propagations in a Cortical Network Model

2003 ◽  
Vol 89 (5) ◽  
pp. 2707-2725 ◽  
Author(s):  
Albert Compte ◽  
Maria V. Sanchez-Vives ◽  
David A. McCormick ◽  
Xiao-Jing Wang
Keyword(s):  
Network Model ◽  
Slow Wave Sleep ◽  
Model Neuron ◽  
Input Resistance ◽  
Oscillatory Activity ◽  
Recurrent Excitation ◽  
Slow Adaptation ◽  
Pharmacological Manipulations

Slow oscillatory activity (<1 Hz) is observed in vivo in the cortex during slow-wave sleep or under anesthesia and in vitro when the bath solution is chosen to more closely mimic cerebrospinal fluid. Here we present a biophysical network model for the slow oscillations observed in vitro that reproduces the single neuron behaviors and collective network firing patterns in control as well as under pharmacological manipulations. The membrane potential of a neuron oscillates slowly (at <1 Hz) between a down state and an up state; the up state is maintained by strong recurrent excitation balanced by inhibition, and the transition to the down state is due to a slow adaptation current (Na+-dependent K+ current). Consistent with in vivo data, the input resistance of a model neuron, on average, is the largest at the end of the down state and the smallest during the initial phase of the up state. An activity wave is initiated by spontaneous spike discharges in a minority of neurons, and propagates across the network at a speed of 3–8 mm/s in control and 20–50 mm/s with inhibition block. Our work suggests that long-range excitatory patchy connections contribute significantly to this wave propagation. Finally, we show with this model that various known physiological effects of neuromodulation can switch the network to tonic firing, thus simulating a transition to the waking state.

Prefrontal Task-Related Activity Representing Visual Cue Location or Saccade Direction in Spatial Working Memory Tasks

2002 ◽  
Vol 87 (1) ◽  
pp. 567-588 ◽  
Author(s):  
Kazuyoshi Takeda ◽  
Shintaro Funahashi
Keyword(s):  
Working Memory ◽  
Prefrontal Cortex ◽  
Spatial Working Memory ◽  
Delay Period ◽  
Neuron Activity ◽  
Delayed Response ◽  
Related Activity ◽  
Visual Cue ◽  
Response Period ◽  
Dorsolateral Prefrontal

To examine what kind of information task-related activity encodes during spatial working memory processes, we analyzed single-neuron activity in the prefrontal cortex while two monkeys performed two different oculomotor delayed-response (ODR) tasks. In the standard ODR task, monkeys were required to make a saccade to the cue location after a 3-s delay, whereas in the rotatory ODR (R-ODR) task, they were required to make a saccade 90° clockwise from the cue location after the 3-s delay. By comparing the same task-related activities in these two tasks, we could determine whether such activities encoded the location of the visual cue or the direction of the saccade. One hundred twenty one neurons exhibited task-related activity in relation to at least one task event in both tasks. Among them, 41 neurons exhibited directional cue-period activity, most of which encoded the location of the visual cue. Among 56 neurons with directional delay-period activity, 86% encoded the location of the visual cue, whereas 13% encoded the direction of the saccade. Among 57 neurons with directional response-period activity, 58% encoded the direction of the saccade, whereas 35% encoded the location of the visual cue. Most neurons whose response-period activity encoded the location of the visual cue also exhibited directional delay-period activity that encoded the location of the visual cue as well. The best directions of these two activities were identical, and most of these response-period activities were postsaccadic. Therefore this postsaccadic activity can be considered a signal to terminate unnecessary delay-period activity. Population histograms encoding the location of the visual cue showed tonic sustained activation during the delay period. However, population histograms encoding the direction of the saccade showed a gradual increase in activation during the delay period. These results indicate that the transformation from visual input to motor output occurs in the dorsolateral prefrontal cortex. The analysis using population histograms suggests that this transformation occurs gradually during the delay period.

Dopamine Modulates Excitability of Basolateral Amygdala Neurons In Vitro

2005 ◽  
Vol 93 (3) ◽  
pp. 1598-1610 ◽  
Author(s):  
Sven Kröner ◽  
J. Amiel Rosenkranz ◽  
Anthony A. Grace ◽  
German Barrionuevo
Keyword(s):  
Basolateral Amygdala ◽  
Neuronal Response ◽  
Brain Slices ◽  
Receptor Activation ◽  
D1 Receptor ◽  
In Vivo Studies ◽  
Projection Neurons ◽  
Direct Effects

The amygdala plays a role in affective behaviors, which are modulated by the dopamine (DA) innervation of the basolateral amygdala complex (BLA). Although in vivo studies indicate that activation of DA receptors alters BLA neuronal activity, it is unclear whether DA exerts direct effects on BLA neurons or whether it acts via indirect effects on BLA afferents. Using whole cell patch-clamp recordings in rat brain slices, we investigated the site and mechanisms through which DA regulates the excitability of BLA neurons. Dopamine enhanced the excitability of BLA projection neurons in response to somatic current injections via a postsynaptic effect. Dopamine D1 receptor activation increased excitability and evoked firing, whereas D2 receptor activation increased input resistance. Current- and voltage-clamp experiments in projection neurons showed that D1 receptor activation enhanced excitability by modulating a 4-aminopyridine- and α-dendrotoxin-sensitive, slowly inactivating K+ current. Furthermore, DA and D1 receptor activation increased evoked firing in fast-spiking BLA interneurons. Consistent with a postsynaptic modulation of interneuron excitability, DA also increased the frequency of spontaneous inhibitory postsynaptic currents recorded in projection neurons without changing release of GABA. These data demonstrate that DA exerts direct effects on BLA projection neurons and indirect actions via modulation of interneurons that may work in concert to enhance the neuronal response to large, suprathreshold inputs, while suppressing weaker inputs.

Sign in / Sign up

Export Citation Format

Share Document