Neurons In Adult Rats Research Articles

Sensory Experience Restructures Thalamocortical Axons during Adulthood

The brain's capacity to rewire is thought to diminish with age. It is widely believed that development stabilizes the synapses from thalamus to cortex and that adult experience alters only synaptic connections between cortical neurons. Here we show that thalamocortical (TC) inputs themselves undergo massive plasticity in adults. We combined whole-cell recording from individual thalamocortical neurons in adult rats with a recently developed automatic tracing technique to reconstruct individual axonal trees. Whisker trimming substantially reduced thalamocortical axon length in barrel cortex but not the density of TC synapses along a fiber. Thus, sensory experience alters the total number of TC synapses. After trimming, sensory stimulation evoked more tightly time-locked responses among thalamorecipient layer 4 cortical neurons. These findings indicate that thalamocortical input itself remains plastic in adulthood, raising the possibility that the axons of other subcortical structures might also remain in flux throughout life.

Fos expression in the FoxP2 and Lmx1b neurons of the parabrachial nucleus following cardiovascular changes

The parabrachial nucleus (PB) is a key brainstem site that receives visceral afferent inputs from the nucleus tractus solitarius, and sends efferent projections to the forebrain. Since the chemical identity of the cardiovascular‐receptive PB neurons remains largely unknown, we used a new approach to define the PB neurons on the basis of their neural lineage. Discrete subpopulations of the PB neurons in adult rats constitutively express the transcription factors Forkhead box protein2 (FoxP2), LIM homeodomain transcription factor 1 beta (Lmx1b), and in some cases, both. Fos‐activation in the PB was analyzed after sustained hypotension or hypertension in conscious rats. Hypotension and hypertension produced similar Fos‐expression patterns. Fos‐activated FoxP2 neurons were found in the dorsal lateral and external lateral PB subgroups and Fos‐activated Lmx1b neurons were concentrated in the medial and external lateral PB regions. Lmx1b activated neurons were present in the dorsomedial PB. Kölliker‐Fuse neurons express both FoxP2 and Lmx1b, and only a few were Fos‐activated after cardiovascular changes. In conclusion, five PB subdivisions (dorsal lateral, dorsal medial, external lateral, and medial, Kölliker‐Fuse) receive cardiovascular information. These data clearly implicate specific PB populations in cardiovascular regulation. Supported by NIH Grants HL‐25449, NS057105, and DA0017371.

Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons

Exposure to alcohol in utero is a well known cause of mental retardation in humans. Using experimental models of fetal alcohol spectrum disorder, it has been demonstrated that cortical pyramidal neurons and their projections are profoundly and permanently impaired. Yet, how the functional features of these cells are modified and how such modifications impact cognitive processes is still unknown. To address this, we studied the intrinsic electrophysiological properties of pyramidal neurons in young adult rats (P30-P60) exposed to ethanol inhalation during the first week of postnatal life (P2-P6). Dual whole-cell recordings from the soma and distal apical dendrites were performed and, following the injection of depolarizing current into the dendrites, layer 5 neurons from ethanol-treated (Et) animals displayed a lower number and a shorter duration of dendritic spikes, attributable to a downregulation of calcium electrogenesis. As a consequence, the mean number of action potentials recorded at the soma after dendritic current injection was also lower in Et animals. No significant differences between Et and controls were observed in the firing pattern elicited in layer 5 neurons by steps of depolarizing somatic current, even though the firing rate was significantly lower in Et animals. The firing pattern and the firing rate of layer 2/3 neurons were not affected by alcohol exposure.

Reelin demarcates a subset of pre‐Bötzinger complex neurons in adult rat

Identification of two markers of neurons in the pre-Bötzinger complex (pre-BötC), the neurokinin 1 receptor (NK1R) and somatostatin (Sst) peptide, has been of great utility in understanding the essential role of the pre-BötC in breathing. Recently, the transcription factor dbx1 was identified as a critical, but transient, determinant of glutamatergic pre-BötC neurons. Here, to identify additional markers, we constructed and screened a single-cell subtractive cDNA library from pre-BötC inspiratory neurons. We identified the glycoprotein reelin as a potentially useful marker, because it is expressed in distinct populations of pre-BötC and inspiratory bulbospinal ventral respiratory group (ibsVRG) neurons. Reelin ibsVRG neurons were larger (27.1 ± 3.8 μm in diameter) and located more caudally (>12.8 mm caudal to Bregma) than reelin pre-BötC neurons (15.5 ± 2.4 μm in diameter, <12.8 mm rostral to Bregma). Pre-BötC reelin neurons coexpress NK1R and Sst. Reelin neurons were also found in the parahypoglossal and dorsal parafacial regions, pontine respiratory group, and ventromedial medulla. Reelin-deficient (Reeler) mice exhibited impaired respones to hypoxia compared with littermate controls. We suggest that reelin is a useful molecular marker for pre-BötC neurons in adult rodents and may play a functional role in pre-BötC microcircuits.

Traumatic Brain Injury in Adult Rats Causes Progressive Nigrostriatal Dopaminergic Cell Loss and Enhanced Vulnerability to the Pesticide Paraquat

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of nigrostriatal dopaminergic neurons and the accumulation of alpha-synuclein. Both traumatic brain injury (TBI) and pesticides are risk factors for PD, but whether TBI causes nigrostriatal dopaminergic cell loss in experimental models and whether it acts synergistically with pesticides is unknown. We have examined the acute and long-term effects of TBI and exposure to low doses of the pesticide paraquat, separately and in combination, on nigrostriatal dopaminergic neurons in adult male rats. In an acute study, rats received moderate TBI by lateral fluid percussion (LFP) injury, were injected with saline or paraquat (10 mg/kg IP) 3 and 6 days after LFP, were sacrificed 5 days later, and their brains processed for immunohistochemistry. TBI alone increased microglial activation in the substantia nigra, and caused a 15% loss of dopaminergic neurons ipsilaterally. Paraquat increased the TBI effect, causing a 30% bilateral loss of dopaminergic neurons, reduced striatal tyrosine hydroxylase (TH) immunoreactivity more than TBI alone, and induced alpha-synuclein accumulation in the substantia nigra pars compacta. In a long-term study, rats received moderate LFP, were injected with saline or paraquat at 21 and 22 weeks post-injury, and were sacrificed 4 weeks later. At 26 weeks post injury, TBI alone induced a 30% bilateral loss of dopaminergic neurons that was not exacerbated by paraquat. These data suggest that TBI is sufficient to induce a progressive degeneration of nigrostriatal dopaminergic neurons. Furthermore, TBI and pesticide exposure, when occurring within a defined time frame, could combine to increase the PD risk.

Nucleolar disruption and apoptosis are distinct neuronal responses to etoposide‐induced DNA damage

Although DNA damaging topoisomerase inhibitors induce apoptosis in developing neurons, their effects on adult neurons have not yet been characterized. We report a blockage of RNA-Polymerase-1-driven transcription and nucleolar stress in neocortical neurons of adult rats after intracarotid injection of the DNA-topoisomerase-2 inhibitor, etoposide. Intracerebroventricular injection of etoposide induced a similar response in neonatal rats. In contrast, etoposide triggered neuronal apoptosis in the neonates, but not the adults. Nucleolar disruption and apoptosis were also observed in etoposide-challenged cultured cortical neurons from newborn rats. In that system, activation of the DNA double strand break signaling kinase ataxia telangiectasia-mutated protein kinase, p53 and p53-dependent apoptosis required lower etoposide concentrations than did the p53-independent induction of nucleolar stress. These distinct responses may be coupled to different forms of etoposide-induced DNA damage. Indeed, double strand breaks by the over-expressed endonuclease I-Ppo1 were sufficient to induce p53-dependent apoptosis. Moreover, nucleolar transcription was insensitive to such damage implying single strand breaks and/or topoisomerase-2-DNA adducts as triggers of nucleolar stress. Because nucleolar stress is not age-restricted, it may underlie non-apoptotic neurotoxicity of chemotherapy- or neurodegeneration-associated DNA damage by reducing ribosomal biogenesis in adult brain. Conversely, nucleolar insensitivity to double strand breaks likely contributes to mature neuron tolerance of such lesions.

Effects of prostaglandin D 2 on tetrodotoxin-resistant Na + currents in DRG neurons of adult rat

Tetrodotoxin-resistant (TTX-R) Na + channels play a key role in the generation of action potentials in nociceptive dorsal root ganglion (DRG) neurons and are an important target for the proinflammatory mediator prostaglandin E 2, which augments these currents. Prostaglandin D 2 (PGD 2) is released in the tissue together with prostaglandin E 2, and it was reported to be antiinflammatory, but its effect on primary afferent neurons is unclear. In the present study we localised G s-protein-coupled DP1 and G i-protein-coupled DP2 receptors in DRG neurons, and we assessed the effect of PGD 2 on TTX-R Na + currents in patch-clamp recordings from small- to medium-sized cultured DRG neurons from adult rats. DP1 and DP2 receptor-like immunoreactivity was localised in the vast majority of DRG neurons. In all neurons, PGD 2 shifted conductance to more hyperpolarised potentials, depending on an action at Na v1.9 channels. In about one third of the neurons, PGD 2 additionally influenced Na v1.8 channels by facilitating conductance and by increasing maximal current amplitudes. Selective DP1 receptor activation increased the amplitude of TTX-R Na + currents of most neurons, but this effect was counteracted by DP2 receptor activation, which by itself had no effect. In the current-clamp mode, PGD 2 lowered the threshold for elicitation of an action potential and increased the number of action potentials per stimulus, an effect mainly depending on DP1 receptor activation. Thus, the net effect of PGD 2 on DRG neurons is pronociceptive, although the magnitude of the TTX-R Na + currents depends on the balance of DP1 and DP2 receptor activation. Prostaglandin D 2 regulates conductance and current amplitudes of tetrodotoxin-resistant sodium channels on dorsal root ganglion neurons by a balanced action at DP1 and DP2 receptor subtypes.

Regulation of synaptic plasticity by hippocampus synthesized estradiol.

Estradiol is synthesized from cholesterol in hippocampal neurons of adult rats by cytochrome P450 and hydroxysteroid dehydrogenase enzymes. These enzymes are expressed in the glutamatergic neurons of the hippocampus. Surprisingly, the concentration of estradiol and androgen in the hippocampus is significantly higher than that in circulation. Locally synthesized estradiol rapidly and potently modulates synaptic plasticity within the hippocampus. E2 rapidly potentiates long-term depression and induces spinogenesis through synaptic estrogen receptors and kinases. The rapid effects of estradiol are followed by slow genomic effects mediated by both estrogen receptors located at the synapse and nucleus, modulating long-term potentiation and promoting the formation of new functional synaptic contacts. Age-related changes in hippocampally derived estradiol synthesis and distribution of estrogen receptors may alter synaptic plasticity, and could potentially contribute to age-related cognitive decline. Understanding factors which regulate hippocampal estradiol synthesis could lead to the identification of alternatives to conventional hormone therapy to protect against age-related cognitive decline.

Effects of acetazolamide on transient K+ currents and action potentials in nodose ganglion neurons of adult rats.

The aim of the present study was to determine whether acetazolamide (AZ) contributes to the inhibition of the fast inactivating transient K+ current (IA) in adult rat nodose ganglion (NG) neurons. We have previously shown that pretreatment with either AZ or 4‐AP attenuated or blocked the CO2‐induced inhibition of slowly adapting pulmonary stretch receptors in in vivo experiments. The patch‐clamp experiments were performed by using the isolated NG neurons. In addition to this, the RT‐PCR of mRNA and the expression of voltage‐gated K+ (Kv) 1.4, Kv 4.1, Kv 4.2, and Kv 4.3 channel proteins from nodose ganglia were examined. We used NG neurons sensitive to the 1 mM AZ application. The application of 1 mM AZ inhibited the IA by approximately 27% and the additional application of 4‐AP (1 mM) further inhibited IA by 48%. The application of 0.1 μM α‐dendrotoxin (α‐DTX), a slow inactivating transient K+ current (ID) blocker, inhibited the baseline IA by approximately 27%, and the additional application of 1 mM AZ further decreased the IA by 51%. In current clamp experiments, AZ application (1 mM) increased the number of action potentials due to the decreased duration of the depolarizing phase of action potentials and/or due to a reduction in the resting membrane potential. Four voltage‐gated K+ channel proteins were present, and most (80–90%) of the four Kv channels immunoreactive neurons showed the co‐expression of carbonic anhydrase‐II (CA‐II) immunoreactivity. These results indicate that the application of AZ causes the reduction in IA via the inhibition of four voltage‐gated K+ channel (Kv) proteins without affecting ID.

Cholecystokinin-8 activates myenteric neurons in 21- and 35-day old but not 4- and 14-day old rats

Cholecystokinin (CCK) activates the myenteric neurons of adult rats. The goal of this work is to determine the ontogeny of this activation by CCK-8 in the myenteric plexus of the duodenum (2 cm immediately following the pyloric sphincter aborally) and compare it with that of the dorsal vagal complex (DVC) – which occurs in 1-day old pups. Despite the existence of both of the CCK receptors, CCK 1 and CCK 2, in 4, 14, 21 and 35 day old rats, CCK-8 (0, 5, 10, 20 and 40 μg/kg, i.p.) increased Fos-like immunoreactivity (Fos-LI, a marker for neuronal activation) in the myenteric neurons of 21- and 35-day old rats but in the DVC of all age groups. As such, this belated activation of myenteric neurons by CCK-8 compared to the DVC may reflect a delayed role for these neurons in CCK-related functions.

Melatonin inhibits microglial activation, reduces pro‐inflammatory cytokine levels, and rescues hippocampal neurons of adult rats with acute Klebsiella pneumoniae meningitis

Acute bacterial meningitis caused by Klebsiella pneumoniae (K.pneumoniae) is a major health threat with a high mortality rate and severe neuro-cognitive sequelae. The intense pro-inflammatory cytokine released from calcium-mediated microglial activation plays an important role in eliciting neuronal damage in the hippocampal region. Considering melatonin possesses anti-inflammatory and immuno-modulatory properties, the present study determined whether melatonin can effectively decrease inflammatory responses and prevent hippocampal damage in animals subjected to K.pneumoniae. Adult rats inoculated with K.pneumoniae received a melatonin injection immediately thereafter at doses of 5, 25, 50, or 100 mg/kg. Following 24 h of survival, all experimental animals were processed for time-of-flight secondary ion mass spectrometry (for detecting glial calcium intensity), isolectin-B4 histochemistry (reliable marker for microglial activation), pro-inflammatory cytokine measurement as well as cytochrome oxidase and in situ dUTP end-labeling (representing neuronal bio-energetic status and apoptotic changes, respectively). Results indicate that in K.pneumoniae-infected rats, numerous calcium-enriched microglia, enhanced pro-inflammatory cytokine, and various apoptotic neurons with low bio-energetic activity were detected in hippocampus. Following melatonin administration, however, all parameters including glial calcium intensity, microglial activation, pro-inflammatory cytokine levels, and number of apoptotic neurons were successfully decreased with maximal change observed at a melatonin dose of 100 mg/kg. Enzymatic data corresponded well with above findings in which all surviving neurons displayed high bio-energetic activity. As effectively reducing glia-mediated inflammatory response is neuro-protective to hippocampal neurons, the present study supports the clinical use of melatonin as a potential therapeutic agent to counteract K.pneumoniae meningitis-induced neuro-cognitive damage.

Postnatal fluoxetine treatment affects the development of serotonergic neurons in rats

The goal of the present study was to investigate morphological changes in the serotonergic neurons/terminals in the dorsal (DR) and median (MnR) raphe nuclei and on the hippocampal dentate gyrus (DG) in neonatal rats treated from the 1st to the 21st postnatal day with fluoxetine (10 mg/kg sc, daily) or drug vehicle (0.9% saline 1 ml/kg). The results show that postnatal chronic treatment with fluoxetine promoted: (1) a smaller body weight increase during the pre-weaning period; (2) smaller number of 5-HT neurons in the DR; (3) smaller 5-HT neuronal cell bodies (area, perimeter and diameter) in the DR and the MnR and (4) diminished serotonergic terminals in the DG. These data suggest that the development of the serotonergic system was impaired and that early exposure to fluoxetine damaged the morphology of 5-HT neurons in young adult rats. While these findings are consistent with other work, more studies are needed to better clarify the effects of postnatal chronic treatment with fluoxetine on the serotonergic system and, consequently, on the functions modulated by serotonin.

PTEN Inhibition to Facilitate Intrinsic Regenerative Outgrowth of Adult Peripheral Axons

In vivo regeneration of peripheral neurons is constrained and rarely complete, and unfortunately patients with major nerve trunk transections experience only limited recovery. Intracellular inhibition of neuronal growth signals may be among these constraints. In this work, we investigated the role of PTEN (phosphatase and tensin homolog deleted on chromosome 10) during regeneration of peripheral neurons in adult Sprague Dawley rats. PTEN inhibits phosphoinositide 3-kinase (PI3-K)/Akt signaling, a common and central outgrowth and survival pathway downstream of neuronal growth factors. While PI3-K and Akt outgrowth signals were expressed and activated within adult peripheral neurons during regeneration, PTEN was similarly expressed and poised to inhibit their support. PTEN was expressed in neuron perikaryal cytoplasm, nuclei, regenerating axons, and Schwann cells. Adult sensory neurons in vitro responded to both graded pharmacological inhibition of PTEN and its mRNA knockdown using siRNA. Both approaches were associated with robust rises in the plasticity of neurite outgrowth that were independent of the mTOR (mammalian target of rapamycin) pathway. Importantly, this accelerated outgrowth was in addition to the increased outgrowth generated in neurons that had undergone a preconditioning lesion. Moreover, following severe nerve transection injuries, local pharmacological inhibition of PTEN or siRNA knockdown of PTEN at the injury site accelerated axon outgrowth in vivo. The findings indicated a remarkable impact on peripheral neuron plasticity through PTEN inhibition, even within a complex regenerative milieu. Overall, these findings identify a novel route to propagate intrinsic regeneration pathways within axons to benefit nerve repair.

Expression of chimeric estrogen-glucocorticoid-receptor in the amygdala reduces anxiety

The basolateral amygdala is critical for generating anxiety, and exposure to glucocorticoids induces anxiety. The demonstrated ability of glucocorticoids to cause dendritic expansion and increase excitability in the amygdala could help mediate the behavioral effects of glucocorticoids, and thus may be important therapeutic target for anxiety. In contrast, estrogen has the opposite effects of glucocorticoids in many domains. In this study, we employed a gene therapeutic approach to reduce anxiety and dendritic arborization of amygdaloid neurons of adult male Wistar rats. We used a herpes simplex viral vector to express a chimeric steroid receptor (“ERGR”) which binds glucocorticoids yet transduces their actions into estrogenic effects. When expressed in the basolateral amygdala (BLA), ERGR reduced anxiety, as tested on elevated plus-maze and open field, without affecting conditioned fear, another amygdala-dependent behavior. Moreover, ERGR also blocked glucocorticoid-induced dendritic expansion of BLA neurons. Thus ERGR expression in the BLA provides a potential therapeutic against anxiety disorders.

Projections of preBötzinger Complex neurons in adult rats

The preBötzinger Complex (preBötC) contains neural microcircuitry essential for normal respiratory rhythm generation in rodents. A subpopulation of preBötC neurons expresses somatostatin, a neuropeptide with a modulatory action on breathing. Acute silencing of a subpopulation of preBötC neurons transfected by a virus driving protein expression under the somatostatin promoter results in persistent apnea in awake adult rats. Given the profound effect of silencing these neurons, their projections are of interest. We used an adeno-associated virus to overexpress enhanced green fluorescent protein driven by the somatostatin promoter in preBötC neurons to label their axons and terminal fields. These neurons send brainstem projections to: 1) contralateral preBötC; 2) ipsi- and contralateral Bötzinger Complex; 3) ventral respiratory column caudal to preBötC; 4) parafacial respiratory group/retrotrapezoid nucleus; 5) parahypoglossal nucleus/nucleus of the solitary tract; 6) parabrachial/Kölliker-Fuse nuclei; and 7) periaqueductal gray. We did not find major projections to either cerebellum or spinal cord. We conclude that there are widespread projections from preBötC somatostatin-expressing neurons specifically targeted to brainstem regions implicated in control of breathing, and provide a network basis for the profound effects and the essential role of the preBötC in breathing.

Experimental acute hyperthyroidism disrupts hippocampal long-term potentiation but not paired pulse facilitation in adult rats

Event Abstract Back to Event Experimental acute hyperthyroidism disrupts hippocampal long-term potentiation but not paired pulse facilitation in adult rats A. S. Artis1*, C. Süer1, N. Dolu1 and L. Sahin1 1 Erciyes University Medical Faculty, Physiology Department, Turkey Manipulations of thyroid hormones have been shown to influence learning and memory. The main paradigm currently used to investigate hyperthyroidism is the administration of thyroxin to adult normothyroid animals. To date, however, there is a lack of electrophysiological data to complement results from behavioral studies. In the present study, we therefore tested the effects of L-thyroxine on paired-pulse facilitation and long-term potentiation in rats. The experiments were carried out on rats between the ages of 9-10 months and were approved by the Erciyes University Committee on Ethics in Animal Experimentation. The experimental animals were randomly divided into a hyperthyroid group and a control group (n=6 in each group). All rats in the hyperthyroid group were injected with thyroxine (0.1 mg/kg/day, ip, 14 days). At the 15th day, stimulating and recording electrodes were introduced in the medial perforant path and dentate gyrus, respectively. Field excitatory postsynaptic potentials (fEPSP) in response to electrical stimulation of perforant pathway were recorded from dentate gyrus using a voltage/current amplifier. fEPSP amplitudes were plotted relative to increasing current of the electrical stimulus to obtain input-output relationship. Paired pulse facilitation was measured from evoked responses of paired pulses with inter-pair intervals between 20-160 ms. Long-term potentiation was induced by four sets of tetanic trains after a baseline recording of fEPSP. Compared to controls, the thyroxine-treated rats showed a significantly attenuated response during input-output relationship and lower efficacy of long-term potentiation. No significant differences were found in paired pulse facilitation. These results provide in vivo evidence that administration of L-thyroxine leads to changes in the excitability of dentate gyrus neurons in adult rats. We hypothesize that this could be due to reduced expression of the NR1-NR2A subgroups of NMDA-type glutamate receptors, which are known to play a role in long term potentiation. To test this hypothesis it will be necessary to combine behavioral and electrophysiological measurements with studies of receptor binding or Western blot analysis. Conference: 2nd NEUROMED Workshop, Fez, Morocco, 10 Jun - 12 Jun, 2010. Presentation Type: Oral Presentation Topic: Oral Session 3: The plastic brain: implications for learning and education Citation: Artis AS, Süer C, Dolu N and Sahin L (2010). Experimental acute hyperthyroidism disrupts hippocampal long-term potentiation but not paired pulse facilitation in adult rats. Front. Neurosci. Conference Abstract: 2nd NEUROMED Workshop. doi: 10.3389/conf.fnins.2010.12.00031 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Jun 2010; Published Online: 04 Jun 2010. * Correspondence: A. S Artis, Erciyes University Medical Faculty, Physiology Department, Kayseri, Turkey, aseda@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers A. S Artis C. Süer N. Dolu L. Sahin Google A. S Artis C. Süer N. Dolu L. Sahin Google Scholar A. S Artis C. Süer N. Dolu L. Sahin PubMed A. S Artis C. Süer N. Dolu L. Sahin Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Injury Induced Activation of Extracellular Signal-Regulated Kinase (ERK) in the Rat Rostral Ventromedial Medulla (RVM) is Age Dependant and Requires the Lamina I Projection Pathway

Descending controls originating in part from the rostral ventromedial medulla (RVM) regulate the excitability of dorsal horn neurons and maintain peripheral pain states. Activation of extracellular signal regulated kinase (ERK) in RVM neurons has been shown following peripheral inflammation and is involved in generating the accompanying inflammatory hyperalgesia. Here, we show that spared nerve injury (SNI), a model of neuropathic pain, results in an increase in ERK activity in RVM neurons of adult rats 3 and 8 days following surgery. We carried out two experimental procedures to demonstrate that this increase in ERK activation was related to the increased mechanical sensitivity associated with SNI. First, we showed that lesions of the lamina I/III ascending pathway from the dorsal horn attenuated both mechanical hyperalgesia and ERK activation in the RVM. Second, we performed SNI in P10 rats. At this age, SNI did not result in mechanical hypersensitivity, as previously shown, and did not activate ERK in the RVM. Finally, the percentage of pERK expressing neurones that were also serotonergic was always around 60%, independent of pain state and age, indicating an important role for serotonin in descending controls of pain states.

Adult-Born Hippocampal Neurons Are More Numerous, Faster Maturing, and More Involved in Behavior in Rats than in Mice

Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared with mature neurons. However, there are conflicting reports on whether or not young neurons contribute to performance in behavioral tasks, and there is no clear relationship between the timing of maturation of young neurons and the duration of neurogenesis reduction in studies showing behavioral deficits. We asked whether these discrepancies could reflect differences in the properties of young neurons in mice and rats. We report that young neurons in adult rats show a mature neuronal marker profile and activity-induced immediate early gene expression 1-2 weeks earlier than those in mice. They are also twice as likely to escape cell death, and are 10 times more likely to be recruited into learning circuits. This comparison holds true in two different strains of mice, both of which show high rates of neurogenesis relative to other background strains. Differences in adult neurogenesis are not limited to the hippocampus, as the density of new neocortical neurons was 5 times greater in rats than in mice. Finally, in a test of function, we find that the contribution of young neurons to fear memory is much greater in rats than in mice. These results reveal substantial differences in new neuron plasticity and function between these two commonly studied rodent species.

Receptive field plasticity of area 17 visual cortical neurons of adult rats

In contrast to somatosensory cortex (SI), where the pervasiveness of reorganizational capacities is well-established, plasticity of receptive fields (RFs) of adult primary visual cortex (VI) remains controversial. To investigate RF plasticity in VI of adult rats, we here used intracortical microstimulation (ICMS) to overcome particularities related to stimulus presentation and training procedures which limit comparison across modalities. Our results show that VI RFs can be altered by ICMS; however, changes depended on the pre-ICMS RF size. Initially small RFs expanded after 2 h of ICMS with little signs of recovery within the next hours, while initially large RFs remained unaffected. Inspection of the time course of neuron responses revealed, however, that in large RFs early response components were enhanced, while late response components were reduced resulting in changes of the spatiotemporal RF properties. Although plastic changes in VI showed a substantial heterogeneity, our results indicate a capacity of VI neurons to undergo plastic changes comparable to SI neurons. However, the magnitude and aspects of reversibility appeared to be different suggesting a significant modality-specificity of reorganizational changes of cortical sensory neurons.

Damage and plasticity in adult rat hippocampal trisynaptic circuit neurons after neonatal exposure to glutamate excitotoxicity

Hippocampal vulnerability to excitotoxicity has been widely studied along with its implication to learning and memory. Neonatal glutamate excitotoxicity induces loss of CA1 pyramidal neurons in adult rats concomitantly with some plastic changes in the dendritic spines of surviving neurons. At least in part, these may underlie the place learning impairments seen in previous studies based on a similar excitotoxicity-inducing model. In the present study, cytoarchitecture of dentate gyrus, CA3 and CA1 fields were evaluated in 120-day-old rats, after they had been neonatally treated with glutamate as monosodium salt. Dentate granule cells and CA1 pyramidal neurons were less than those counted in NaCl-treated control animals. In addition, dentate granule cells had more dendrites as well as more branched spines. Spine density in CA1 pyramidal neurons was greater than in the controls. Additionally, thin and mushroom spines were proportionally more abundant in monosodium glutamate-treated animals. No effects were seen in the hippocampal CA3 field. Our results strongly suggest a long-term induction of plastic changes in the cytoarchitecture of the hippocampal trisynaptic circuit neurons after cell death provoked by the monosodium glutamate-induced excitotoxicity. These plastic events as well as the aberrant expression of the glutamate NMDA receptors resulting from monosodium glutamate neonatal treatment could be strongly associated with the place learning impairments previously reported.