Computational Studies of Gain Modification by Serotonin in Pyramidal Neurons of Prefrontal Coxtex

2006 ◽  
Author(s):  
Guoshi Li ◽  
Harvey C. Cline ◽  
Pierre Blier ◽  
Satish Nair
Keyword(s):  
Prefrontal Cortex ◽  
Firing Rate ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Input Resistance ◽  
Square Root ◽  
Gain Modulation ◽  
Cellular Mechanisms ◽  
Brain Functions ◽  
A Current

Serotonin (5-HT) is widely implicated in brain functions and diseases, but the cellular mechanisms underlying 5-HT functions in the brain are not well understood (Zhang and Arsenault, 2005). Recent experiments (Zhang and Arsenault, 2005) have shown that 5-HT substantially increased the slope (gain) of the firing rate current (F-I) curve in layer 5 pyramidal neurons of the rat prefrontal cortex and this effect was limited to the range of firing rate (0-10 Hz) that is known to behaviourally relevant. Furthermore, it was found that 5-HT mediated gain increase was due to a reduction of the afterhyperpolarization (AHP) and an induction of the slow afterdepolarization (ADP), regardless of changes in the membrane potential, the input resistance or the properties of action potentials. To investigate this frequency-dependent gain modulation of 5-HT on the prefrontal cortex neurons, conductance-based Hodgkin-Huxley type models of the regular spiking (RS) cells in the prefrontal cortex are developed using a step by step approach. We first show that a model with an A current displays a square-root form F-I curve with higher slope at low frequency. However, for the same range of current injection steps used in experiment, the frequency range goes beyond 20 Hz, suggesting the presence of other hyperpolarizing currents in the model. As suggested by the experiment (Zhang and Arsenault, 2005), AHP currents (fast AHP, medium AHP and slow AHP) are included in the model to simulate 5-HT effect. Simulations show that AHP currents effectively linearize the F-I curve and decrease the slope of F-I curve in general, thus reducing the neuronal excitability. Since the slow AHP current is a target of 5-HT, the strength of this current is reduced gradually and the F-I curves are plotted together for comparison. The results indicate that with decreasing slow AHP strength, the current thresholds for repetitive spiking decreases and the slopes of the F-I curves increase in general. A square-root form F-I curve is not evident until the slow AHP current is blocked completely. This suggests that the medium AHP current also play a role in linearizing the F-I curve besides the slow AHP current. Based on current findings, a full model with both A current and AHP currents is being constructed to match the experimental data more closely so the mechanism of 5-HT on gain modulation of prefrontal cortical neurons can be better understood.

scholarly journals Dopamine Increases Excitability of Pyramidal Neurons in Primate Prefrontal Cortex

2000 ◽  
Vol 84 (6) ◽  
pp. 2799-2809 ◽  
Author(s):  
Darrell A. Henze ◽  
Guillermo R. González-Burgos ◽  
Nathaniel N. Urban ◽  
David A. Lewis ◽  
German Barrionuevo
Keyword(s):  
Prefrontal Cortex ◽  
Action Potential ◽  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Input Resistance ◽  
Initiation Site ◽  
D1 Receptor ◽  
Resting Membrane Potential ◽  
Cellular Mechanisms

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 ( n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 μM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 μM) but not significantly altered by the D2 antagonist sulpiride (2.5 μM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.

Activation of Metabotropic Glutamate 2/3 Receptors Reverses the Effects of NMDA Receptor Hypofunction on Prefrontal Cortex Unit Activity in Awake Rats

2005 ◽  
Vol 93 (4) ◽  
pp. 1989-2001 ◽  
Author(s):  
Houman Homayoun ◽  
Mark E. Jackson ◽  
Bita Moghaddam
Keyword(s):  
Prefrontal Cortex ◽  
Nmda Receptor ◽  
Firing Rate ◽  
Spike Activity ◽  
Systemic Exposure ◽  
Nmda Antagonist ◽  
Laboratory Animals ◽  
Cellular Mechanisms ◽  
Physiological Basis ◽  
Metabotropic Glutamate

Systemic exposure to N-methyl-d-aspartate (NMDA) receptor antagonists can lead to psychosis and prefrontal cortex (PFC)–dependent behavioral impairments. Agonists of metabotropic glutamate 2/3 (mGlu2/3) receptors ameliorate the adverse behavioral effects of NMDA antagonists in humans and laboratory animals, and are being considered as a novel treatment for some symptoms of schizophrenia. Despite the compelling behavioral data, the cellular mechanisms by which potentiation of mGlu2/3 receptor function attenuates the effects of NMDA receptor hypofunction remain unclear. In freely moving rats, we recorded the response of medial PFC (prelimbic) single units to treatment with the NMDA antagonist MK801 and assessed the dose-dependent effects of pre- or posttreatment with the mGlu2/3 receptor agonist LY354740 on this response. NMDA receptor antagonist-induced behavioral stereotypy was measured during recording because it may relate to the psychotomimetic properties of this treatment and is dependent on the functional integrity of the PFC. In most PFC neurons, systemic administration of MK801 increased the spontaneous firing rate, decreased the variability of spike trains, and disrupted patterns of spontaneous bursts. Given alone, LY354740 (1, 3, and 10 mg/kg) decreased spontaneous activity of PFC neurons at the highest dose. Pre- or posttreatment with LY354740 blocked MK801-induced changes on firing rate, burst activity, and variability of spike activity. These physiological changes coincided with a reduction in MK801-induced behavioral stereotypy by LY354740. These data indicate that activation of mGlu2/3 receptors reduces the disruptive effects of NMDA receptor hypofunction on the spontaneous spike activity and bursting of PFC neurons. This mechanism may provide a physiological basis for reversal of NMDA antagonist-induced behaviors by mGlu2/3 agonists.

scholarly journals Maturation of Layer V Pyramidal Neurons in the Rat Prefrontal Cortex: Intrinsic Properties and Synaptic Function

2004 ◽  
Vol 91 (3) ◽  
pp. 1171-1182 ◽  
Author(s):  
Zhong-wei Zhang
Keyword(s):  
Prefrontal Cortex ◽  
Time Constant ◽  
Pyramidal Neurons ◽  
Rapid Development ◽  
Input Resistance ◽  
Synaptic Function ◽  
Resting Potential ◽  
Intrinsic Properties ◽  
Patch Clamp Recording ◽  
Layer V

Layer V pyramidal neurons in the rat medial prefrontal cortex (PFC) were examined with whole cell patch-clamp recording in acute slices from postnatal day 1 (P1) to P36. In the first few days after birth, layer V pyramidal neurons had low resting potentials, high-input resistance, and long membrane time constant. During the next 2 wk, the resting potential shifted by -14 mV, while the input resistance and time constant decreased by 15- and 4-fold, respectively. Between P3 and P21, the surface area of the cell body doubled, while the total lengths of apical and basal dendrites increased by 5- and 13-fold, respectively. Action potentials (APs) were observed at all aged tested. The peak amplitude of APs increased by 30 mV during the first 3 wk, while AP rise time and half-maximum duration shortened significantly. Compared with neurons at P21 or older, neurons in the first week required much smaller currents to reach their maximum firing frequencies, but the maximum frequencies were lower than those at older ages. Stimulation of layer II/III induced monosynaptic responses in neurons older than P5. Paired-pulse responses showed a short-term depression at P7, which shifted progressive to facilitation at older ages. These results demonstrate that, similar to other neurons in the brain, layer V pyramidal neurons in the PFC undergo a period of rapid development during the first 3 wk after birth. These findings suggest that the intrinsic properties of neurons and the properties of synaptic inputs develop concomitantly during early life.

scholarly journals Layer- and subregion-specific differences in the neurophysiological properties of rat medial prefrontal cortex pyramidal neurons

2018 ◽  
Vol 119 (1) ◽  
pp. 177-191 ◽  
Author(s):  
Chenghui Song ◽  
James R. Moyer
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Conditioned Fear ◽  
Input Resistance ◽  
Underlying Mechanism ◽  
Fear Memory ◽  
Membrane Properties ◽  
Spike Threshold ◽  
Memory Acquisition

Medial prefrontal cortex (mPFC) is critical for the expression of long-term conditioned fear. However, the neural circuits involving fear memory acquisition and retrieval are still unclear. Two subregions within mPFC that have received a lot of attention are the prelimbic (PL) and infralimbic (IL) cortices (e.g., Santini E, Quirk GJ, Porter JT. J Neurosci 28: 4028–4036, 2008; Song C, Ehlers VL, Moyer JR Jr. J Neurosci 35: 13511–13524, 2015). Interestingly, PL and IL may play distinct roles during fear memory acquisition and retrieval but the underlying mechanism is poorly understood. One possibility is that the intrinsic membrane properties differ between these subregions. Thus, the current study was carried out to characterize the basic membrane properties of mPFC neurons in different layers and subregions. We found that pyramidal neurons in L2/3 were more hyperpolarized and less excitable than in L5. This was observed in both IL and PL and was associated with an enhanced h-current in L5 neurons. Within L2/3, IL neurons were more excitable than those in PL, which may be due to a lower spike threshold and higher input resistance in IL neurons. Within L5, the intrinsic excitability was comparable between neurons obtained in IL and PL. Thus, the heterogeneity in physiological properties of mPFC neurons may underlie the observed subregion-specific contribution of mPFC in cognitive function and emotional control, such as fear memory expression. NEW & NOTEWORTHY This is the first study to demonstrate that medial prefrontal cortical (mPFC) neurons are heterogeneous in both a layer- and a subregion-specific manner. Specifically, L5 neurons are more depolarized and more excitable than those neurons in L2/3, which is likely due to variations in h-current. Also, infralimbic neurons are more excitable than those of prelimbic neurons in layer 2/3, which may be due to differences in certain intrinsic properties, including input resistance and spike threshold.

Dynamic Spatiotemporal Synaptic Integration in Cortical Neurons: Neuronal Gain, Revisited

2005 ◽  
Vol 94 (4) ◽  
pp. 2785-2796 ◽  
Author(s):  
Rony Azouz
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Temporal Integration ◽  
Synaptic Integration ◽  
Neuronal Membrane ◽  
Network Dynamic ◽  
Alternative Mechanism ◽  
Gain Modulation ◽  
Voltage Gated ◽  
The Relationship

Gain modulation is a ubiquitous phenomenon in cortical neurons, providing flexibility to operate under changing conditions. The prevailing view is that this modulation reflects a change in the relationship between mean input and output firing rate brought about by variation in neuronal membrane characteristics. An alternative mechanism is proposed for neuronal gain modulation that takes into account the capability of cortical neurons to process spatiotemporal synaptic correlations. Through the use of numerical simulations, it is shown that voltage-gated and leak conductances, membrane potential, noise, and input firing rate modify the sensitivity of cortical neurons to the degree of temporal correlation between their synaptic inputs. These changes are expressed in a change of the temporal window for synaptic integration and the range of input correlation over which response probability is graded. The study also demonstrates that temporal integration depends on the distance between the inputs and that this interplay of space and time is modulated by voltage-gated and leak conductances. Thus, gain modulation may reflect a change in the relationship between spatiotemporal synaptic correlations and output firing probability. It is further proposed that by acting synergistically with the network, dynamic spatiotemporal synaptic integration in cortical neurons may serve a functional role in the formation of dynamic cell assemblies.

scholarly journals Cell-type specific D1 dopamine receptor modulation of projection neurons and interneurons in the prefrontal cortex

2018 ◽  
Author(s):  
Paul G. Anastasiades ◽  
Christina Boada ◽  
Adam G. Carter
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
D1 Receptor ◽  
Receptor Expression ◽  
D1 Receptors ◽  
Projection Neurons ◽  
Specific Cell ◽  
Action Potential Firing ◽  
Receptor Modulation

ABSTRACTDopamine modulation in the prefrontal cortex (PFC) mediates diverse effects on neuronal physiology and function, but the expression of dopamine receptors at sub-populations of pyramidal neurons and interneurons remains unresolved. Here, we examine D1 receptor expression and modulation at specific cell types and layers in the mouse prelimbic PFC. We first show that D1 receptors are enriched in pyramidal neurons in both layers 5 and 6, and that these cells project intra-telencephalically, rather than to sub-cortical structures. We then find that D1 receptors are also present in interneurons, and enriched in VIP+ interneurons that co-expresses calretinin, but absent from PV+ and SOM+ interneurons. Finally, we determine that D1 receptors strongly and selectively enhance action potential firing in only a subset of these cortico-cortical neurons and VIP+ interneurons. Our findings define several novel sub-populations of D1+ neurons, highlighting how modulation via D1 receptors can influence both excitatory and disinhibitory micro-circuits in the PFC.

scholarly journals Astroglial CD38 regulates social memory and synapse formation through SPARCL1 in the medial prefrontal cortex

2021 ◽  
Author(s):  
TSUYOSHI HATTORI ◽  
Stanislav M Cherepanov ◽  
Ryo Sakaga ◽  
Jureepon Roboon ◽  
Dinh Thi Nguyen ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Social Behavior ◽  
Medial Prefrontal Cortex ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Synapse Formation ◽  
Neural Circuit ◽  
Social Memory ◽  
Behavioral Abnormalities ◽  
Survival And Reproduction

Social behavior is essential for the health, survival and reproduction of animals, yet the role of astrocytes in social behavior is largely unknown. CD38 is critical for social behaviors by regulating oxytocin release from hypothalamic neurons. On the other hand, CD38 is most abundantly expressed in astrocytes especially in the postnatal cortex, and is important for astroglial development. Here, we demonstrate that astroglial CD38 plays a pivotal role in the social behavior. Selective deletion of CD38 in postnatal astrocytes, but not in adult astrocytes, specifically impaired social memory without any other behavioral abnormalities. Morphological analysis revealed reductions in spine numbers, mature spines and excitatory synapse numbers in the pyramidal neurons of the medial prefrontal cortex (mPFC) due to deletion of astroglial CD38 in the postnatal brain. Astrocyte-conditioned medium (ACM) of CD38 KO astrocytes reduced synaptogenesis of cortical neurons by reducing extracellular SPARCL1, a synaptogenic protein. Finally, the release of SPARCL1 from astrocytes is regulated by CD38/cADPR/calcium signaling. Our data indicate that astroglial CD38 developmentally regulates social memory and neural circuit formation in the developing brain by promoting synaptogenesis through SPARCL1.

scholarly journals Parvalbumin-Positive Basket Interneurons in Monkey and Rat Prefrontal Cortex

2008 ◽  
Vol 100 (4) ◽  
pp. 2348-2360 ◽  
Author(s):  
N. V. Povysheva ◽  
A. V. Zaitsev ◽  
D. C. Rotaru ◽  
G. Gonzalez-Burgos ◽  
D. A. Lewis ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Cortical Neurons ◽  
Input Resistance ◽  
Cell Types ◽  
Threshold Current ◽  
Electrophysiological Properties ◽  
Basket Cells ◽  
Physiological Properties ◽  
Axonal Arbor ◽  
Fast Spiking

Differences in the developmental origin and relative proportions of biochemically distinct classes of cortical neurons have been found between rodents and primates. In addition, species differences in the properties of certain cell types, such as neurogliaform cells, have also been reported. Consequently, in this study we compared the anatomical and physiological properties of parvalbumin (PV)-positive basket interneurons in the prefrontal cortex of macaque monkeys and rats. The somal size, total dendritic length, and horizontal and vertical spans of the axonal arbor were similar in monkeys and rats. Physiologically, PV basket cells could be identified as fast-spiking interneurons in both species, based on their short spike and high-frequency firing without adaptation. However, important interspecies differences in the intrinsic physiological properties were found. In monkeys, basket cells had a higher input resistance and a lower firing threshold, and they generated more spikes at near-threshold current intensities than those in rats. Thus monkey basket cells appeared to be more excitable. In addition, rat basket cells consistently fired the first spike with a substantial delay and generated spike trains interrupted by quiescent periods more often than monkey basket cells. The frequency of miniature excitatory postsynaptic potentials in basket cells was considerably higher in rats than that in monkeys. These differences between rats and monkeys in the electrophysiological properties of PV-positive basket cells may contribute to the differential patterns of neuronal activation observed in rats and monkeys performing working-memory tasks.

scholarly journals Repeated cocaine exposure increases fast-spiking interneuron excitability in the rat medial prefrontal cortex

2013 ◽  
Vol 109 (11) ◽  
pp. 2781-2792 ◽  
Author(s):  
Emilie Campanac ◽  
Dax A. Hoffman
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Pyramidal Neurons ◽  
Input Resistance ◽  
Compensatory Mechanism ◽  
Cocaine Exposure ◽  
Membrane Excitability ◽  
Chronic Cocaine ◽  
Fast Spiking ◽  
Circuit Output

The medial prefrontal cortex plays a key role in cocaine addiction. However, how chronic cocaine exposure affects cortical networks remains unclear. Most studies have focused on layer 5 pyramidal neurons (the circuit output), while the response of local GABAergic interneurons to cocaine remains poorly understood. Here, we recorded from fast-spiking interneurons (FS-IN) after repeated cocaine exposure and found altered membrane excitability. After cocaine withdrawal, FS-IN showed an increase in the number of spikes evoked by positive current injection, increased input resistance, and decreased hyperpolarization-activated current. We also observed a reduction in miniature excitatory postsynaptic currents, whereas miniature inhibitory postsynaptic current activity was unaffected. We show that, in animals with cocaine history, dopamine receptor D2 activation is less effective in increasing FS-IN intrinsic excitability. Interestingly, these alterations are only observed 1 wk or more after the last cocaine exposure. This suggests that the dampening of D2-receptor-mediated response may be a compensatory mechanism to rein down the excitability of FS-IN.

Modulation of Firing Rate by Background Synaptic Noise Statistics in Rat Visual Cortical Neurons

2010 ◽  
Vol 104 (5) ◽  
pp. 2792-2805 ◽  
Author(s):  
Michael P. Sceniak ◽  
Shasta L. Sabo
Keyword(s):  
Firing Rate ◽  
Cortical Neurons ◽  
Pyramidal Neurons ◽  
Statistical Properties ◽  
Neuronal Firing ◽  
Synaptic Conductance ◽  
System Response ◽  
Temporal Delay ◽  
Synaptic Noise ◽  
Synaptic Conductances

It has been shown previously that background synaptic noise modulates the response gain of neocortical neurons. However, the role of the statistical properties of the noise in modulating firing rate is not known. Here, the dependence of firing rate on the statistical properties of the excitatory to inhibitory balance (EI) in cortical pyramidal neurons was studied. Excitatory glutamatergic and inhibitory GABAergic synaptic conductances were simulated as two stochastic processes and injected into individual neurons in vitro through use of the dynamic-clamp system. Response gain was significantly modulated as a function of the statistical interactions between excitatory and inhibitory synaptic conductances. Firing rates were compared for noisy synaptic conductance steps by varying either the EI correlation or the relative delay between correlated E and I. When inhibitory synaptic conductances exhibited a short temporal delay (5 ms) relative to correlated excitatory synaptic conductances, the response gain was increased compared with noise with no temporal delay but with an equivalent degree of correlation. The dependence of neuronal firing rate on the EI delay of the noisy background synaptic conductance suggests that individual excitatory pyramidal neurons are sensitive to the EI balance of the synaptic conductance. Therefore the statistical EI interactions encoded within the synaptic subthreshold membrane fluctuations are able to modulate neuronal firing properties.

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