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Treatment with melatonin is routinely prescribed for its potent antioxidant and cognitive‐promoting effects, nevertheless, it has yet to find neuromodulatory effects in normal and disease conditions. Therefore, to investigate its neuromodulatory mechanisms, melatonin was systemically administered over 10 consecutive days to both intracortical normal saline‐ and amyloid‐β 1‐42 (Aβ) peptide‐injected rats. At the behavioral level, treatment with melatonin was associated with reduced efficacy in restoring Aβ‐induced deficit in passive‐avoidance memory. Whole‐cell patch‐clamp recordings from CA1 pyramidal neurons revealed that melatonin treatment reduced spontaneous and evoked intrinsic excitability in control rats while exerting a reduction of spontaneous, but not evoked activity, in the Aβ‐injected group. Interestingly, treatment with melatonin enhances after‐hyperpolarization in control, but not Aβ‐injected rats. In contrast, our voltage‐clamp study showed that Ih current is significantly enhanced by Aβ injection, and this effect is further strengthened by treatment with melatonin in Aβ‐injected rats. Finally, we discovered that the transcription of melatonin receptors 1 (MT1) and 2 (MT2) is significantly upregulated in the hippocampi of Aβ‐injected rats. Collectively, our study demonstrates that systemic treatment with melatonin has differential neuromodulation on CA1 neuronal excitability, at least in part, via differential effects on after‐hyperpolarization and Ih currents due to Aβ‐induced neurotoxicity. Summary: The molecular and cellular underpinnings of AD pathology are accompanied by developing aberrant neuronal excitability. These neuronal properties are also a part of melatonin effectors by which melatonin exerts its cognitive‐promoting and anti‐seizure effects. In this paper, we answer the question of how melatonin may influence neuronal excitability in healthy and AD‐like conditions. Answering this query is important considering the fact that melatonin effectiveness is altered with the development of AD. This may be due to, as we demonstrate, the deregulation of melatonin receptors in the hippocampus of AD rats. These findings are significant because shed further light on the cellular mechanisms of melatonin and help us to understand AD pathophysiology. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is associated with epileptiform activity in the hippocampus; however, the underlying mechanisms have not been fully determined. The goal was to understand what changes take place in intrinsic neuronal physiology in the hippocampus after blunt force trauma to the cortex. In this context, hyperpolarization‐activated cation current (Ih) currents may have a critical role in modulating the neuronal intrinsic membrane excitability; therefore, its contribution to the TBI‐induced hyperexcitability was assessed. In a model of TBI caused by controlled cortical impact (CCI), the intrinsic electrophysiological properties of pyramidal neurons were examined 1 week after TBI induction in rats. Whole‐cell patch‐clamp recordings were performed under current‐ and voltage‐clamp conditions following ionotropic receptors blockade. Induction of TBI caused changes in the intrinsic excitability of pyramidal neurons, as shown by a significant increase and decrease in firing frequency and in the rheobase current, respectively (p <.05). The evoked firing rate and the action potential time to peak were also significantly increased and decreased, respectively (p <.05). In the TBI group, the amplitude of instantaneous and steady‐state Ih currents was both significantly smaller than those in the control group (p <.05). The Ih current density was also significantly decreased (p <.001). Findings indicated that TBI led to an increase in the intrinsic excitability in CA1 pyramidal neurons and changes in Ih current could be, in part, one of the underlying mechanisms involved in this hyperexcitability. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is undoubtedly one of the serious and growing public health challenges in the world today. There is an unmet need for new and effective preventative and therapeutic treatment approaches for AD, particularly at early stages of the disease. However, the underlying mechanism against Aβ-induced electrophysiological alteration in cultured hippocampal pyramidal neurons is still not fully understood. This study investigated the impacts of activation and inhibition of PPAR-γ/δ on the Aβ-induced functional toxicity, which occured before cell death, using patch clamp technique. Findings demonstrated that Aβ treatment alone altered the normal electrophysiological properties and reduced the Ca2+ channel currents in primary cultured hippocampal pyramidal neurons without any major changes either in cell structure, as evidenced by electron microscope examination, or cell viability. Rosiglitazone (30 μM), a potent PPAR-γ activator, when co-treated with Aβ (100 nM) prevented almost completely the induction of function toxicity of Aβ, as evidentiated by restored normal appearing electrophysiological properties. Inhibition of PPAR- γ/δ by FH535 (15 μM), an inhibitor of both Wnt/beta-catenin signaling and PPAR- γ and δ activity, when applied in combination of Aβ not only worsen the toxic electrophysiological effects of Aβ on firing frequency, membrane resistance and cell viability, but also even preserved the suppressive effect of Aβ on Ca2+ channel current when compared to control condition. Overall, these findings suggest that PPAR-γ activation could be a potential candidate to prevent the functional changes induced by low concentration of Aβ which may possibly occur in neurons during early stages of AD. [ABSTRACT FROM AUTHOR]

Introduction: Although aging is the most important risk factor for Alzheimer's disease (AD), there is evidence indicating that neuroinflammation may contribute to the development and progression of the disease. Several studies indicated that minocycline may exert neuroprotective effects in rodent models of neurodegenerative diseases. Nevertheless, there are also other studies implying that minocycline has no positive beneficial effects. Thus, the aim of the present study was to assess the preventive effect of minocycline against Aβ-induced changes in intrinsic electrophysiological properties in a rat model of AD. Methods: The present study extended this line of research by examining whether inhibition of microglial activation may alter the intrinsic electrophysiological properties of CA1 pyramidal neurons in a rat model of Aβ neurotoxicity, using whole cell patch clamp. Results: Findings showed that bilateral injection of the Aβ (1-42) into the prefrontal cortex caused membrane hyperpolarization, action potential (AP) narrowing and after hyperpolarization (AHP) amplitude enhancement. It was also resulted in a faster decay time of AP, higher rheobase current, lower firing frequency and smaller post stimulus AHP amplitude. Administration of minocycline (45mg/kg, i.p) not only failed to prevent Aβ-induced alterations in the intrinsic electrophysiological properties, but also enhanced the effects of Aβ on neuronal firing behavior. Conclusion: It can be concluded that minocycline, as a microglial inhibitor, may enhance the disruption of electrophysiological properties of CA1 pyramidal neurons induced by Aβ neurotoxin, including AP parameters and intrinsic neuronal excitability. [ABSTRACT FROM AUTHOR]

Introduction: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-β peptides (Aβ) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following Aβ injection. Furthermore, Nissl staining showed that Aβ neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Aβ treated rats. Moreover, higher NF-κB immunoreactive CA1 pyramidal neurons were remarkably observed in Aβ treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Aβ-induced increased NF-κB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of Aβ into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by Aβ. [ABSTRACT FROM AUTHOR]

In this study, the effect of repetitive transcranial magnetic stimulation (rTMS) on the kindling induced changes in electrophysiological firing properties of hippocampal CA1 pyramidal neurons was investigated. Male Wistar rats were kindled by daily electrical stimulation of the basolateral amygdala in a semi-rapid manner (12 stimulations/day) until they achieved stage-5 seizure. One group (kindled+rTMS (KrTMS)) of animals received rTMS (240 pulses at 1 Hz) at 5 min after termination of daily kindling stimulations. Twenty-four hours following the last kindling stimulation electrophysiological properties of hippocampal CA1 pyramidal neurons were investigated using a whole-cell patch clamp technique, under current clamp condition. Amygdala kindling significantly decreased the adaptation index, post-afterhyperpolarization, rheobase current, utilization time, and delay to the first rebound spike. It also caused an increase in the voltage sag, number of rebound spikes and number of evoked action potential. Results of the present study revealed that application of rTMS following kindling stimulations had antiepileptogenic effects. In addition, application of rTMS prevented hyperexcitability of CA1 pyramidal neurons induced by kindling and conserved the normal neuronal firing. [ABSTRACT FROM AUTHOR]

Introduction: Considering the antiepileptogenic effects of repeated transcranial magnetic stimulation (rTMS), the effect of rTMS applied during amygdala kindling on spontaneous activity of hippocampal CA1 pyramidal neurons was investigated. Materials and Methods: A tripolar electrode was inserted in basolateral amygdala of Male Wistar rats. After a recovery period, animals received daily kindling stimulations until they reached stage 5 seizure. In one group of animals, rTMS at frequency of 1 Hz were applied to hippocampus once daily at 5 min after termination of kindling stimulations. 24 h after the last kindling stimulation, spontaneous activity of CA1 pyramidal neurons of the hippocampus was investigated using whole cell patch clamp technique. Results: Kindling-induced seizures resulted in increment of spontaneous activity of hippocampal CA1 neurons, but application of rTMS during amygdala kindling prevented it. Moreover, rTMS administration inhibited the kindling-induced enhancement of afterdepolarization (ADP) amplitude and action potential duration. Conclusion: Results of this study suggest that rTMS exerts its anticonvulsant effect, in part, through preventing the amygdala kindling-induced increase in spontaneous activity and excitability of hippocampal CA1 pyramidal neurons. [ABSTRACT FROM AUTHOR]

• Capacity of synapses to express synaptic plasticity changes in PTZ-kindled animals. • Glial cells are involved in PTZ-induced metaplasticity. • Inhibition of glial cells reduces metaplasticity and subsequent epileptic behavior. Epilepsy is characterized by the unpredictability but recurrence of seizures caused by the synchronized aberrant firing of neuronal populations. It has been shown that astrocytes (one of the most prominent glial cells) are ideally positioned to induce or contribute to neural network synchronization. Although astrocytes cannot generate action potentials, they have the capacity to sense and respond to neuronal activity, which allows them to function as homeostatic regulators of synaptic interactions. Considering the necessity of astrocyte-neuron bidirectional interactions in synaptic transmission and plasticity, in the current study, the role of astrocytes in synaptic metaplasticity and resultant behavioral seizures induced by Pentylentetrazole (PTZ) was assessed. Rats were kindled by intraperitoneal (i.p.) injection of PTZ (30 mg/kg/48 h). A glial cell inhibitor, Fluorocitrate (FC), was injected into the right lateral cerebral ventricle of the rat 30 min before PTZ during kindling progress. The maximal seizure stage (SS), stage 2 and 4 latency (S2L, S4L), stage 4 and 5 duration (S4D, S5D), and seizure duration (SD) were all assessed 20 min after PTZ administration by observation. Following Schaffer collateral stimulation, in vivo field, potential recordings from the CA1 area of the hippocampus were employed to assess the metaplasticity induced in kindled rats. The inhibition of glial cells during the kindling process significantly lowered SS, S4D&S5D and increased S4L (Two-way ANOVA, Bonferroni Posttest, P < 0.05, P < 0.01, and P < 0.001). In comparison to the control group, electrophysiological data demonstrated that HFS-induced LTP in kindled animals was decreased (Unpaired t -test, P < 0.05). Glial cell inhibition prevented PTZ's effect on LTP. Our data imply that kindling altered CA1 pyramidal neurons' vulnerability to synaptic plasticity. This shift in neuronal plasticity (metaplasticity) is mediated in part by glial cells and is important in the formation of seizure symptoms. As a result, glial cell inhibition was found to alleviate seizure behavior. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by alterations and imbalances in multiple brain neurochemical systems, particularly the serotonergic neurotransmission. This includes changes in serotonin (5-HT) levels, aberrations in 5-HT transporter activity, and decreased synthesis and expression of 5-HT receptors (5-HT7Rs). The exact role of the brain 5-HT system in the development of ASD remains unclear, with conflicting evidence on its involvement. Recently, we have reported research has shown a significant decrease in serotonergic neurons originating from the raphe nuclei and projecting to the CA1 region of the dorsal hippocampus in autistic-like rats. Additionally, we have shown that chronic activation of 5-HT7Rs reverses the effects of autism induction on synaptic plasticity. However, the functional significance of 5-HT7Rs at the cellular level is still not fully understood. This study presents new evidence indicating an upregulation of 5-HT7R in the CA1 subregion of the hippocampus following the induction of autism. The present account also demonstrates that activation of 5-HT7R with its agonist LP-211 can reverse electrophysiological abnormalities in hippocampal pyramidal neurons in a rat model of autism induced by prenatal exposure to VPA. Additionally, in vivo administration of LP-211 resulted in improvements in motor coordination, novel object recognition, and a reduction in stereotypic behaviors in autistic-like offspring. The findings suggest that dysregulated expression of 5-HT7Rs may play a role in the pathophysiology of ASD, and that agonists like LP-211 could potentially be explored as a pharmacological treatment for autism spectrum disorder. • Upregulation of 5-HT7 receptors may be correlated with induction of autistic traits. • Dysregulated 5-HT7R expression induces neuronal hyperexcitability in autistic rats. • Activating 5-HT7R expression eliminates autism-induced neuronal hyperresponsiveness. • 5-HT7R activation reduces motor imbalance & stereotypic behavior in autistic-like rats. • 5-HT7R activation rescues short-term memory recognition in autistic-like offspring. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurological disease that slowly causing memory impairments with no effective treatment. We have recently reported that kisspeptin-13 (KP-13) ameliorates Aβ toxicity-induced memory deficit in rats. Here, the possible cellular impact of kisspeptin receptor activation in a rat model of the early stage AD was assessed using whole-cell patch-clamp recording from CA1 pyramidal neurons and molecular approaches. Compared to neurons from the control group, cells from the Aβ-treated group displayed spontaneous and evoked hyperexcitability with lower spike frequency adaptation. These cells had also a lower sag ratio in response to hyperpolarizing prepulse current delivered before a depolarizing current injection. Neurons from the Aβ-treated group exhibited short spike onset latency, lower rheobase and short utilization time compared with those in the control group. Furthermore, phase plot analysis of action potential showed that Aβ treatment affected the action potential features. These electrophysiological changes induced by Aβ were associated with increased expression of stromal interaction molecules (STIMs), particularly (STIM2) and decreased pCREB/CREB ratio. Treatment with KP-13 following Aβ injection into the entorhinal cortex, however, prevented the excitatory effect of Aβ on spontaneous and evoked neuronal activity, increased the latency of onset, enhanced the sag ratio, increased the rheobase and utilization time, and prevented the changes induced Aβ on spike parameters. In addition, the KP-13 application after Aβ treatment reduced the expression of STIMs and increased the pCREB/CREB ratio compared to those receiving Aβ treatment alone. In summary, these results provide evidence that activation of kisspeptin receptor may be effective against pathology of Aβ. • kisspeptin-13 prevented the Aβ-induced hyperexcitability in CA1 pyramidal neurons. • kisspeptin-13 treatment prevented Aβ-induced hippocampal overexpression of STIMs. • kisspeptin-13 treatment prevented the decreasing effect of Aβ on pCREB/CREB ratio. [ABSTRACT FROM AUTHOR]

Social hierarchy is a fundamental feature of social organization that can influence brain and emotional processing regarding social ranks. Several areas, including the medial prefrontal cortex (mPFC), the hippocampus, and the basolateral nucleus of the amygdala (BLA), are recognized to be involved in the regulation of emotional processing. However, its delicate structural correlates in brain regions are poorly understood. To address this issue, social hierarchy in home-caged sibling Wistar rats (three male rats/cage) was determined by employing a social confrontation tube test (postnatal weeks 9–12). Then, locomotor activity and anxiety-like behaviors were evaluated using an open-field test (OFT) and elevated plus-maze (EPM) at 13 weeks of age. The rapid Golgi impregnation method was conducted to quantify the spine density of the first secondary branch of the primary dendrite in 20 µm length. The results indicated that dominant rats had significantly higher anxiety-like behaviors compared to subordinates, as was evident by lower open-arm entries and time spent in the EPM and lower entries and time spent in the center of OFT. The spine density analysis revealed a significantly higher number of spines in subordinates compared to the dominant rats in dmPFC pyramidal neurons and the apical and basal dendrites of hippocampal CA1 pyramidal neurons. However, the spine density of pyramidal-like neurons in the BLA was higher in dominant rats. Our findings suggest that dominant social rank is associated with higher anxiety and differential density of the dendritic spine in the prefrontal cortex and limbic regions of the brain in male rats. [Display omitted] • Dominant position was associated with higher anxiety-like behaviors. • Structural study of social ranks without inducing stress was done in sibling male rats. • The spine density in the dmPFC and CA1 of dominant rats were lower than subordinates. • The number of spines in the BLA was higher in Dominant rats. [ABSTRACT FROM AUTHOR]

[Display omitted] • The role of α-adrenergic receptors in anti-epileptiform action of LFS was studied. • LFS reduced the neuronal hyperexcitability following epileptiform activity. • α-Receptor antagonists restored LFS' effect on action potential threshold to increase. • α-Adrenergic receptors had role in LFS effect of restoring neuronal excitability. The Inhibitory effect of electrical low-frequency stimulation (LFS) on neuronal excitability and seizure occurrence has been indicated in experimental models, but the precise mechanism has not established. This investigation was intended to figure out the role of α 1 and α 2 adrenergic receptors in LFS' inhibitory effect on neuronal excitability. Epileptiform activity induced in an in vitro rat hippocampal slice preparation by high K+ ACSF and LFS (900 square wave pulses at 1 Hz) was administered at the beginning of epileptiform activity to the Schaffer collaterals. In CA1 pyramidal neurons, the electrophysiological properties were measured at the baseline, before high K+ ACSF washout, and at 15 min after high K+ ACSF washout using whole-cell, patch-clamp recording. Results indicated that after high K+ ACSF washout, prazosine (10 µM; α 1 adrenergic receptor antagonist) and yohimbine (5 µM; α 2 adrenergic receptor antagonist) suppressed the LFS' effect of reducing rheobase current and utilization time following depolarizing ramp current, the latency to the first spike following a depolarizing current and latency to the first rebound action potential following hyperpolarizing current pulses. Thus, it may be proposed that LFS' inhibitory action on the neuronal hyperexcitability, in some way, is mediated by α 1 and α 2 adrenergic receptors. [ABSTRACT FROM AUTHOR]

Low-frequency stimulation has demonstrated promising seizure suppression in animal models of epilepsy, while the mechanism of the effect is still debated. Changes in intrinsic properties have been recognized as a prominent pathophysiologically relevant feature of numerous neurological disorders including epilepsy. Here, it was evaluated whether LFS can preserve the intrinsic neuronal electrophysiological properties in a rat model of epilepsy, focusing on the possible involvement of voltage-gated Ca2+ channels. The amygdala kindling model was induced by 3 s monophasic square wave pulses (50 Hz, 1 ms duration, 12times/day at 5 min intervals). Both LFS alone and kindled plus LFS (KLFS) groups received four packages of LFS (each consisting of 200 monophasic square pulses, 0.1 ms pulse duration at 1 Hz with the after discharge threshold intensity), which in KLFS rats was applied immediately after kindling induction. Whole-cell patch-clamp recordings were made in the presence of fast synaptic blockers 24 h after the last kindling stimulations or following kindling stimulations plus LFS application. In the KLFS group, both the rebound excitation and kindling-induced intrinsic hyperexcitability were decreased, associated with a regular intrinsic firing as indicated by a lower coefficient of variation. The amplitude of afterdepolarization (ADP) and its area under the curve were both decreased in the KLFS group compared to the kindled group. LFS prevented the increasing effect of kindling on Ca2+ currents in the KLFS group. Findings provided evidence for a novel form of epileptiform activity suppression by LFS in the presence of synaptic blockade possibly by decreasing Ca2+ currents. Unlabelled Image • Amygdala kindling alters intrinsic excitability of CA1 pyramidal neurons • Low-frequency stimulation (LFS) prevents the induction of neuronal intrinsic hyperexcitability by amygdala kindling. • Induction of amygdala kindling enhances Ca2 + channel current in CA1 pyramidal neurons • LFS prevented the increasing effect of epileptiform activity on Ca2+ currents. [ABSTRACT FROM AUTHOR]

Highlights • Prenatal exposure to VPA increased autism-like behaviors. • CA1 pyramidal neurons from autistic rats showed hyperexcitability with lower rheobase. • Maternal VPA exposure resulted in a reduction in sag ratio and Ih current. • Maternal exposure to VPA during pregnancy increased the membrane input resistance. • Prenatal exposure to VPA reduced the soma size of pyramidal neurons in offspring. Abstract Autism spectrum disorder (ASD) is a common neuropsychiatric disorder, which is characterized by impairment in social interaction and cognitive behaviors. However, there is not much electrophysiological data available on alterations of neuronal excitability in autism. Here, we assessed the pattern of neuronal excitability and the possible contribution of Ih current to the altered excitability of hippocampal CA1 pyramidal neurons in a rat model of VPA-induced ASD-like behavior. Pregnant Wistar rats received valproic acid (VPA, 500 mg/kg) at gestational day 12.5. All offspring were subjected to behavioral tests to verify the induction of ASD-like behaviors. On postnatal day (PND) 45, whole-cell patch-clamp recordings were performed on hippocampal CA1 pyramidal neurons in slices obtained from control and prenatal VPA-exposed pups, under current and voltage-clamp conditions. Our results showed that beside the induction of behavioral abnormalities in ASD pups, higher excitability of hippocampal CA1 pyramidal neurons was also prominent, as evidenced by a significant increase in the spontaneous firing frequency and evoked firing rate, as well as a significant decrease in the rheobase current. In the VPA-exposed group, the steady-state (ISS) Ih current amplitude was significantly smaller than control cells. The Ih half-activation voltage shifted toward more negative potentials in the VPA-exposed group. The sag ratio was also significantly less than the control cells. Moreover, the cell soma size was shifted toward smaller diameter in VPA-exposed group. Overall, induction of ASD-like behaviors was associated with neuronal hyperexcitability, which, at least in part, could be attributed to the changes in Ih channels function. [ABSTRACT FROM AUTHOR]

Objective: Resveratrol, a phytoalexin, has a wide range of desirable biological actions. Despite a growing body of evidence indicating that resveratrol induces changes in neuronal function, little effort, if any, has been made to investigate the cellular effect of resveratrol treatment on intrinsic neuronal properties. Materials and Methods: This experimental study was performed to examine the acute effects of resveratrol (100 μM) on the intrinsic evoked responses of rat Cornu Ammonis (CA1) pyramidal neurons in brain slices, using whole cell patch clamp recording under current clamp conditions. Results: Findings showed that resveratrol treatment caused dramatic changes in evoked responses of pyramidal neurons. Its treatment induced a significant (P<0.05) increase in the after hyperpolarization amplitude of the first evoked action potential. Resveratrol-treated cells displayed a significantly broader action potential (AP) when compared with either control or vehicle-treated groups. In addition, the mean instantaneous firing frequency between the first two action potentials was significantly lower in resveratrol-treated neurons. It also caused a significant reduction in the time to maximum decay of AP. The rheobase current and the utilization time were both significantly greater following resveratrol treatment. Neurons exhibited a significantly depolarized voltage threshold when exposed to resveratrol. Conclusion: Results provide direct electrophysiological evidence for the inhibitory effects of resveratrol on pyramidal neurons, at least in part, by reducing the evoked neural activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • In VPA-exposed rats CA1 pyramidal neurons displayed enhanced intrinsic electrical responses. • Prenatal VPA-exposed offspring displayed a higher nociceptive threshold. • Prenatal VPA exposure impaired short-term novel object recognition memory. • VPA-exposed group showed altered intrinsic evoked action potentials waveform. • NADPH-diaphorase activity increased in the CA1 region in VPA-exposed offspring. Autism spectrum disorder is a neurodevelopmental disorder characterized by sensory abnormalities, social skills impairment and cognitive deficits. Although recent evidence indicated that induction of autism-like behavior in animal models causes abnormal neuronal excitability, the impact of autism on neuronal properties is still an important issue. Thus, new findings at the cellular level may shed light on the pathophysiology of autism and may help to find effective treatment strategies. Here, we investigated the behavioral, electrophysiological and histochemical impacts of prenatal exposure to valproic acid (VPA) in rats. Findings revealed that VPA exposure caused a significant increase in the hot plate response latency. The novel object recognition ability was also impaired in VPA-exposed rats. Along with these behavioral alterations, neurons from VPA-exposed animals exhibited altered excitability features in response to depolarizing current injections relative to control neurons. In the VPA-exposed group, these changes consisted of a significant increase in the amplitude, evoked firing frequency and the steady-state standard deviation of spike timing of action potentials (APs). Moreover, the half-width, the AHP amplitude and the decay time constant of APs were significantly decreased in this group. These changes in the evoked electrophysiological properties were accompanied by intrinsic hyperexcitability and lower spike-frequency adaptation and also a significant increase in the number of NADPH-diaphorase stained neurons in the hippocampal CA1 area of the VPA-exposed rats. Taken together, findings demonstrate that abnormal nociception and recognition memory is associated with alterations in the neuronal responsiveness and nitrergic system in a rat model of autism-like. [ABSTRACT FROM AUTHOR]