Bi-directional changes in synaptic plasticity induced at corticostriatal synapses in vitro

Long-term changes in the synaptic efficacy of corticostriatal synapses are believed to be important for regulating the excitatory input to the basal ganglia, and hence for motor learning and certain forms of cognition. Previous reports have suggested that long-term depression (LTD) is the predominant form of plasticity at corticostriatal synapses. However, we report here that tetanic stimulation of the white matter can readily induce long-term potentiation (LTP) at corticostriatal synapses in a sagittal slice preparation. Furthermore, we find that corticostriatal LTP is obtained in the absence of pharmacological manipulation, and is dependent on NMDA receptor activation. In contrast, LTD is rarely observed following tetanic stimulation of the white matter, but in fact requires direct stimulation within the striatum. This striatally induced depression is blocked by both D1 and D2 dopamine receptor antagonists and by NMDA receptor blockade. Pairing of striatal stimulation with tetanic stimulation of the white matter does not prevent the induction, but significantly enhances the magnitude of LTP at corticostriatal synapses. We suggest that the corticostriatal depression reported here most likely involves the recruitment of local striatal circuits and dopaminergic inputs, and thus might explain the predominance of LTD previously reported. Our observation that it is indeed possible to induce LTP at corticostriatal synapses under physiological conditions in vitro has implications for the normal function and control of the basal ganglia in motor learning and cognition.     

Substantia nigra dopamine regulates synaptic plasticity and membrane potential fluctuations in the rat neostriatum, in vivo

The spiny projection neurons of the neostriatum are a site at which dopamine inputs from the substantia nigra converge with excitatory inputs from the cerebral cortex. These two systems interact in certain learning and motor control mechanisms of the brain. We investigated these interactions using intracellular recording from spiny striatal neurons in urethane-anaesthetized rats. We found that acute dopamine depletion was associated with long-term depression of corticostriatal synaptic input. Electrical stimulation of the cortex which mimicked synchronous cortical input to striatal neurons also induced long-term depression of corticostriatal inputs. In intact control animals, but not in dopamine-depleted animals, this depression was prevented or reversed by concomitant stimulation of the substantia nigra. In agreement with previous in vitro studies, our in vivo findings show that long-term depression occurs in the corticostriatal pathway, and in addition show that it is regulated by dopaminergic inputs from the substantia nigra. This form of synaptic plasticity may therefore be important for understanding disturbances of the motor system seen in humans with Parkinson's disease.     

Olfactory learning induces differential long-lasting changes in rat central olfactory pathways

In the present work, we investigated lasting changes induced by olfactory learning at different levels of the olfactory pathways. For this, evoked field potentials induced by electrical stimulation of the olfactory bulb were recorded simultaneously in the anterior piriform cortex, the posterior piriform cortex, the lateral entorhinal cortex and the dentate gyrus. The amplitude of the evoked field potential's main component was measured in each site before, immediately after, and 20 days after completion of associative learning. Evoked field potential recordings were carried out under two experimental conditions in the same animals: awake and anesthetized. In the learning task, rats were trained to associate electrical stimulation of one olfactory bulb electrode with the delivery of sucrose (positive reward), and stimulation of a second olfactory bulb electrode with the delivery of quinine (negative reward). In this way, stimulation of the same olfactory bulb electrodes used for inducing field potentials served as a discriminative cue in the learning paradigm. The data showed that positively reinforced learning resulted in a lasting increase in evoked field potential amplitude restricted to posterior piriform cortex and lateral entorhinal cortex. In contrast, negatively reinforced learning was mainly accompanied by a decrease in evoked field potential amplitude in the dentate gyrus. Moreover, the expression of these learning-related changes occurred to be modulated by the animals arousal state. Indeed, the comparison between anesthetized versus awake animals showed that although globally similar, the changes were expressed earlier with respect to learning, under anesthesia than in the awake state. From these data we suggest that associative olfactory learning involves different neural circuits depending on the acquired value of the stimulus. Furthermore, they show the existence of a functional dissociation between anterior and posterior piriform cortex in mnesic processes, and stress the importance of the animal's arousal state on the expression of learning-induced plasticity.     

Spatial performance in a complex maze is associated with persistent long-term potentiation enhancement in mouse hippocampal slices at early training stages

Long-term potentiation (LTP) and long-term depression (LTD) are principal reflections of synaptic plasticity that have been implicated in learning and memory. We have previously shown that spatial learning in a newly validated complex maze is accompanied by depression of hippocampal CA1 synaptic activity in hippocampal slices of trained mice ("behavioral LTD"). In the present study, we investigated whether behavioral LTD is accompanied by alterations of subsequent LTP induced by high-frequency stimulation (HFS). Moreover, we were interested in the time course of such alterations in relation to training stage. Animals underwent 1, 2, and 8 days of spatial training in the complex maze, respectively. Hippocampal slices were taken 24 h after the last training session. We found a simultaneous decrease of basal synaptic response and increase of HFS induced LTP magnitude compared with slices of untrained animals. Synaptic plasticity was not influenced by repeated running wheel exercise in an additional control group without spatial learning. The mentioned alterations occurred already after day 2 of maze exploration parallel to the most pronounced improvement of behavioral performance but did not change thereafter until day 8 despite further learning progress. They were also found when animals were trained for 2 days and kept at rest for a subsequent 6 days. In conclusion, spatial learning may be reflected by distinct and persistent measurable alterations of synaptic plasticity in hippocampal CA1 neurons at early training stages.     

Altered long-term corticostriatal synaptic plasticity in transgenic mice overexpressing human CU/ZN superoxide dismutase (GLY(93)-->ALA) mutation

Apart from the extensive loss of motor neurons, degeneration of midbrain dopaminergic cells has been described in both familial and sporadic forms of amyotrophic lateral sclerosis (ALS). Mice overexpressing the mutant human Cu/Zn superoxide dismutase (SOD1) show an ALS-like phenotype in that they show a progressive death of motor neurons accompanied by degeneration of dopaminergic cells. To describe the functional alterations specifically associated with this dopaminergic dysfunction, we have investigated the corticostriatal synaptic plasticity in mice overexpressing the human SOD1 (SOD1+) and the mutated (Gly(93)-->Ala) form (G93A+) of the same enzyme. We show that repetitive stimulation of the corticostriatal pathway generates long-term depression (LTD) in SOD1+ mice and in control (G93A-/SOD1-) animals, whereas in G93A+ mice the same stimulation generates an N-methyl-D-aspartic acid receptor-dependent long-term potentiation. No significant alterations were found in the intrinsic membrane properties of striatal medium spiny neurons and basal corticostriatal synaptic transmission of G93A+ mice. Bath perfusion of dopamine or the D(2) dopamine receptor agonist quinpirole restored LTD in G93A+ mice. Consistent with these in vitro results, habituation of locomotor activity and striatal-dependent active avoidance learning were impaired in G93A+ mice. Thus, degeneration of dopaminergic neurons in the substantia nigra of G93A+ mice causes substantial modifications in striatal synaptic plasticity and related behaviors, and may be a cellular substrate of the extrapyramidal motor and cognitive disorders observed in familial and sporadic ALS.     

Photic-induced sensitization: eye-specific neural plasticity and effect of behavioral state

We reported previously that exposure to repetitive visual stimulation in ordinary adult rats results in acquisition of an enduring increase in magnitude and change in character of visual cortical responses. This sensitization is consistent with experience-dependent neuroplastic changes, but could also reflect alterations in response with behavioral state during testing. The aim of this study was to distinguish the contributions of behavioral state and neural plasticity in this photic-induced sensitization. We used repetitive light-emitting diode flashes delivered monocularly and recorded electrocorticographically in the albino rat in which retino-geniculo-cortical projections are predominantly crossed. This enabled comparison of visual responses of sensitized visual circuitry associated with one eye to responses from effectively unsensitized circuitry associated with the second eye at similar time points in an animal, thus providing an internal control for behavioral state. Following sensitization, monocular stimulation of one eye produced the characteristic high amplitude driven spike-wave response in corresponding contralateral visual cortex, but not ipsilateral cortex. Expression of the sensitized driven response was optimal in the quiet awake state and suppressed during active exploration, drowsiness, or anesthesia. When the animal was in the quiet awake state, producing sensitized responses to stimulation of the first eye, no such response was observed on alternate trials upon stimulation of the second eye. Only after extended exposure of the second eye did the high amplitude driven spike-wave response in contralateral visual cortex develop. The data further suggest some degree of sensitization of ipsilateral pathways may accompany monocular stimulation and that effects of monocular sensitization could include suppression in pathways related to the unstimulated eye. Thus, while behavioral state influences expression of the sensitized driven visual response, the eye-specific nature of the effect provides strong evidence that response enhancement reflects neuroplasticity in visual pathways and not a more general change in behavioral state during testing.     

Skilled-learning-induced potentiation in rat sensorimotor cortex: a transient form of behavioural long-term potentiation

The relation between the acquisition of a skilled motor task and synaptic plasticity in the sensorimotor cortex of the awake, freely behaving rat was examined. Skilled-motor training was previously found to induce a functional reorganization of the caudal forelimb area, and to induce an increase in synaptic efficacy, measured in vitro, on the side contralateral to the reaching forelimb. Here, we repeatedly measured neocortical evoked potential recordings in awake, freely behaving rats to examine whether skilled training would induce changes in polysynaptic efficacy on the side contralateral to the reaching forelimb. We found that the increase in task proficiency, but not the acquisition of task requirements or the maintenance of task proficiency, induced an increase in synaptic efficacy on the side contralateral to the reaching forelimb. We also tested the hypothesis that skilled learning induced potentiation shares similar mechanisms to long-term potentiation (LTP) and long-term depression by artificially manipulating polysynaptic efficacy in skilled rats with high- and low-frequency stimulation. We observed that, compared with the ipsilateral side, less potentiation but more depression could be induced on the side contralateral to the reaching forelimb. We conclude that a transient, network-based LTP-like mechanism operates during the learning of a skilled motor task.     

Multiple spine boutons are formed after long-lasting LTP in the awake rat

The formation of multiple spine boutons (MSBs) has been associated with cognitive abilities including hippocampal-dependent associative learning and memory. Data obtained from cultured hippocampal slices suggest that the long-term maintenance of synaptic plasticity requires the formation of new synaptic contacts on pre-existing synapses. This postulate however, has never been tested in the awake, freely moving animals. In the current study, we induced long-term potentiation (LTP) in the dentate gyrus (DG) of awake adult rats and performed 3-D reconstructions of electron micrographs from thin sections of both axonal boutons and dendritic spines, 24 h post-induction. The specificity of the observed changes was demonstrated by comparison with animals in which long-term depression (LTD) had been induced, or with animals in which LTP was blocked by an N-methyl-d-aspartate (NMDA) antagonist. Our data demonstrate that whilst the number of boutons remains unchanged, there is a marked increase in the number of synapses per bouton 24 h after the induction of LTP. Further, we demonstrate that this increase is specific to mushroom spines and not attributable to their division. The present investigation thus fills the gap existing between behavioural and in vitro studies on the role of MSB formation in synaptic plasticity and cognitive abilities.     

Reorganization in awake rat auditory cortex by local microstimulation and its effect on frequency-discrimination behavior

In common with other sensory cortices, the mammalian primary auditory cortex (AI) demonstrates the capacity for large-scale reorganization following many experimental situations. For example, training animals in frequency-discrimination tasks has been shown to result in an increase in cortical frequency representation. Such central changes-most commonly, an increase in central representation of specific stimulus parameters-have been hypothesized to underlie the improvements in perceptual acuity (perceptual learning) seen in many learning situations. The actual behavioral relevance of central reorganizations, however, remains speculative. Here, we directly examine this issue. We first show that stimulating the AI cortex of the awake rat with a weak electric current (intracortical microstimulation or ICMS) has the effect of inducing central reorganizations similar to those accompanying the traditional plasticity experiments (a result previously noted only in anesthetized preparations). Depending on the site of AI stimulation, ICMS enlarged the cortical representation of certain frequencies. Next we examined the direct perceptual consequences of ICMS-induced AI reorganization for the rat's ability to discriminate frequencies. Over the course of the experiment, we also detailed, and made comparisons between, the frequency-response characteristics of rat AI cortex in the awake and ketamine-anesthetized animal. AI cells that responded to pure tones were divided into two categories--strongly and weakly responsive--based on the strength of their evoked discharge. Individual cells maintained their respective response strengths in both awake and anesthetized conditions. Strongly responsive cells showed at least four different temporal responses and tended to be narrowly tuned. Their responses were stable over the long term. In general frequency-response characteristics were qualitatively similar in the anesthetized and awake animal; bandwidths tended to be broader in awake animals. Although both strong and weak cell populations respond to tones, only the strongly responsive cells fit into a tonotopically organized scheme. By contrast, weakly responsive cells did not exhibit a frequency mapping and may represent a more diffuse input to AI than that underlying strongly responsive cells. In general, the overall frequency organization of AI was found to be equally well expressed in both the awake and anesthetized rat. ICMS reorganization of AI did not alter frequency-discrimination behavior in the rat--either signal detectability or response bias--suggesting that an increase in central representation, by itself, is insufficient to account for perceptual learning. It is likely that cortical reorganizations that accompany perceptual learning are strongly keyed to specific behavioral contexts.     

Short-term behavioral and electrophysiological consequences of underwater trauma

In a previous work we found that a 30-s underwater trauma, following 8 days of training for a spatial memory task in the water maze, resulted in poor performance in the spatial memory task at both 1 h and 3 weeks after the trauma. Here we found that compared with naive animals and animals that were trained for the spatial learning task but were not traumatized, the traumatized rats showed impaired performance in a spatial learning task in the water maze 20 min after the trauma and a reduced level of dentate gyrus long-term potentiation (LTP) 40 min after high-frequency stimulation to the perforant path. We also found a positive correlation between the behavioral performance and hippocampal plasticity. The reduced ability to induce LTP suggests that the trauma-related behavioral impairment is mediated by hippocampal-dependent processes. The underwater trauma may provide an important and potentially powerful model for understanding the mechanisms underlying the relationship between stress, cognition, and learning.     

Modulation of long-term synaptic plasticity at excitatory striatal synapses

Modulation of long-term plasticity by both the intrinsic activation of metabotropic glutamate receptors and dopamine released from the nigrostriatal pathway was investigated at excitatory striatal synapses. Intracellular recordings demonstrated that tetanic stimulation at an intensity equal to that used for synaptic sampling produced, on average, a slight long-term depression of excitatory postsynaptic potentials. The long-term response pattern was variable, however, with some cells showing potentiation and others no plasticity. Block of metabotropic glutamate receptors with 3-aminophosphonovaleric acid changed the pattern of responses, increasing the percentage of cells showing long-term potentiation. Similarly, 6-hydroxydopamine lesions to the substantia nigra changed the pattern of response to tetanic stimulation, increasing the expression of long-term potentiation. These data indicate that metabotropic glutamate receptor and dopamine receptor activation may function to regulate the expression of activity-dependent plasticity at corticostriatial synapses. Paired-pulse stimulation revealed that post-tetanic plasticity was negatively correlated with changes in paired-pulse plasticity in the control and 6-hydroxydopamine-lesioned groups, suggesting that the expression of long-term plasticity has a presynaptic component at corticostriatal synapses.     

A single day of ethanol exposure during development has persistent effects on bi-directional plasticity, N-methyl-D-aspartate receptor function and ethanol sensitivity

To determine factors that contribute to the learning deficits observed in individuals with fetal alcohol syndrome, we examined the effects of early postnatal ethanol exposure on forms of synaptic plasticity thought to underlie memory. Treatment of rat pups with ethanol on postnatal day 7 impaired the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation and abolished homosynaptic long-term depression in the CA1 region of hippocampal slices prepared at postnatal day 30. An N-methyl-D-aspartate receptor-independent form of long-term potentiation induced by very high frequency stimulation could be induced in slices from ethanol-treated rats. Defects in long-term depression correlated with a diminished contribution of ifenprodil-sensitive N-methyl-D-aspartate receptors to synaptic transmission and defects in a spontaneous alternation behavioral task. Rats exposed to ethanol on postnatal day 7 also exhibited diminished sensitivity of synaptic N-methyl-D-aspartate receptors to block by ethanol at postnatal day 30 and decreased behavioral sedation to systemic ethanol injections. These results indicate that changes in synaptic plasticity and N-methyl-D-aspartate receptor function are likely to provide a neural substrate for the cognitive and behavioral changes that follow developmental ethanol exposure.     

Skilled motor learning does not enhance long-term depression in the motor cortex in vivo

Learning of motor skills may occur as a consequence of changes in the efficacy of synaptic connections in the primary motor cortex. We investigated if learning in a reaching task affects the excitability, short-term plasticity, and long-term plasticity of horizontal connections in layers II-III of the motor cortex. Because training in this task requires animals to be food-deprived, we compared the trained animals with similarly food-deprived untrained animals and normal controls. The results show that the excitability, short-term plasticity, and long-term plasticity of the studied horizontal connections were unaffected by motor learning. However, stress-related effects produced by food deprivation and handling significantly enhanced the expression of long-term depression in these pathways. These results are compatible with the hypothesis that the acquisition of a complex motor skill produces bi-directional changes in synaptic strength that are distributed throughout the complex neural networks of motor cortex, which remains synaptically balanced during learning. The results are incompatible with the idea that learning causes large unidirectional changes in the population response of these neural networks, which may occur instead during certain behavioral states, such as stress.     

Loss of bidirectional striatal synaptic plasticity in L-DOPA-induced dyskinesia

Long-term treatment with the dopamine precursor levodopa (L-DOPA) induces dyskinesia in Parkinson's disease (PD) patients. We divided hemiparkinsonian rats treated chronically with L-DOPA into two groups: one showed motor improvement without dyskinesia, and the other developed debilitating dyskinesias in response to the treatment. We then compared the plasticity of corticostriatal synapses between the two groups. High-frequency stimulation of cortical afferents induced long-term potentiation (LTP) of corticostriatal synapses in both groups of animals. Control and non-dyskinetic rats showed synaptic depotentiation in response to subsequent low-frequency synaptic stimulation, but dyskinetic rats did not. The depotentiation seen in both L-DOPA-treated non-dyskinetic rats and intact controls was prevented by activation of the D1 subclass of dopamine receptors or inhibition of protein phosphatases. The striata of dyskinetic rats contained abnormally high levels of phospho[Thr34]-DARPP-32, an inhibitor of protein phosphatase 1. These results indicate that abnormal information storage in corticostriatal synapses is linked with the development of L-DOPA-induced dyskinesia.     

Alterations in corticostriatal synaptic plasticity in mice overexpressing human α-synuclein

Most forms of Parkinson's disease (PD) are sporadic in nature, but some have genetic causes as first described for the α-synuclein gene. The α-synuclein protein also accumulates as insoluble aggregates in Lewy bodies in sporadic PD as well as in most inherited forms of PD. The focus of the present study is the modulation of synaptic plasticity in the corticostriatal pathway of transgenic (Tg) mice that overexpress the human α-synuclein protein throughout the brain (ASOTg). Paired-pulse facilitation was detected in vitro by activation of corticostriatal afferents in ASOTg mice, consistent with a presynaptic effect of elevated human α-synuclein. However basal synaptic transmission was unchanged in ASOTg, suggesting that human α-synuclein could impact paired-pulse facilitation via a presynaptic mechanism not directly related to the probability of neurotransmitter release. Mice lacking α-synuclein or those expressing normal and A53T human α-synuclein in tyrosine hydroxylase-containing neurons showed, instead, paired-pulse depression. High-frequency stimulation induced a presynaptic form of long-term depression solely in ASOTg striatum. A presynaptic, N-methyl-d-aspartate receptor-independent form of chemical long-term potentiation induced by forskolin (FSK) was enhanced in ASOTg striatum, while FSK-induced cAMP levels were reduced in ASOTg synaptoneurosome fractions. Overall the results suggest that elevated human α-synuclein alters presynaptic plasticity in the corticostriatal pathway, possibly reflecting a reduction in glutamate at corticostriatal synapses by modulation of adenylyl cyclase signaling pathways. ASOTg mice may recapitulate an early stage in PD during which overexpressed α-synuclein dampens corticostriatal synaptic transmission and reduces movement.     

Sensory input directs spatial and temporal plasticity in primary auditory cortex.

The cortical representation of the sensory environment is continuously modified by experience. Changes in spatial (receptive field) and temporal response properties of cortical neurons underlie many forms of natural learning. The scale and direction of these changes appear to be determined by specific features of the behavioral tasks that evoke cortical plasticity. The neural mechanisms responsible for this differential plasticity remain unclear partly because important sensory and cognitive parameters differ among these tasks. In this report, we demonstrate that differential sensory experience directs differential plasticity using a single paradigm that eliminates the task-specific variables that have confounded direct comparison of previous studies. Electrical activation of the basal forebrain (BF) was used to gate cortical plasticity mechanisms. The auditory stimulus paired with BF stimulation was systematically varied to determine how several basic features of the sensory input direct plasticity in primary auditory cortex (A1) of adult rats. The distributed cortical response was reconstructed from a dense sampling of A1 neurons after 4 wk of BF-sound pairing. We have previously used this method to show that when a tone is paired with BF activation, the region of the cortical map responding to that tone frequency is specifically expanded. In this report, we demonstrate that receptive-field size is determined by features of the stimulus paired with BF activation. Specifically, receptive fields were narrowed or broadened as a systematic function of both carrier-frequency variability and the temporal modulation rate of paired acoustic stimuli. For example, the mean bandwidth of A1 neurons was increased (+60%) after pairing BF stimulation with a rapid train of tones and decreased (-25%) after pairing unmodulated tones of different frequencies. These effects are consistent with previous reports of receptive-field plasticity evoked by natural learning. The maximum cortical following rate and minimum response latency were also modified as a function of stimulus modulation rate and carrier-frequency variability. The cortical response to a rapid train of tones was nearly doubled if BF stimulation was paired with rapid trains of random carrier frequency, while no following rate plasticity was observed if a single carrier frequency was used. Finally, we observed significant increases in response strength and total area of functionally defined A1 following BF activation paired with certain classes of stimuli and not others. These results indicate that the degree and direction of cortical plasticity of temporal and receptive-field selectivity are specified by the structure and schedule of inputs that co-occur with basal forebrain activation and suggest that the rules of cortical plasticity do not operate on each elemental stimulus feature independently of others.     

Differential brain-derived neurotrophic factor expression in limbic brain regions following social defeat or territorial aggression

Syrian hamsters readily form dominant-subordinate relationships under laboratory conditions. Winning or losing in agonistic encounters can have striking, long-term effects on social behavior, but the mechanisms underlying this experience-induced behavioral plasticity are unclear. The present study tested the hypothesis that changes in brain-derived neurotrophic factor (BDNF) may at least in part mediate this plasticity. Male hamsters were paired for 15-min using a resident-intruder model, and individuals were identified as winners or losers on the basis of their behavior. BDNF was examined with in situ hybridization 2 hr after treatment during the consolidation period of emotional learning. Losing animals had significantly more BDNF mRNA in the basolateral (BLA) and medial (MeA) nuclei of the amygdala when compared with winning animals as well as novel cage and home cage controls. Interestingly, winning animals had significantly more BDNF mRNA in the dentate gyrus of the dorsal hippocampus than did losing animals, novel, and home cage controls. No conflict-related changes in BDNF mRNA were observed in several other regions including the bed nucleus of the stria terminalis and central amygdala. Next, we demonstrated that K252a, a Trk receptor antagonist, significantly reduced the acquisition of conditioned defeat when administered within the BLA. These data support a model in which BDNF-mediated plasticity within the BLA supports learning of submission or subordinate social status in losing animals, whereas BDNF-mediated plasticity within the hippocampus may instantiate aspects of winning such as control of a territory in dominant animals.     

Long-term potentiation in the rat hippocampus is reversibly depressed by chronic intermittent ethanol exposure

Alcohol exposure induces multiple neuroadaptive changes in the CNS that can have serious long-term consequences on CNS function including cognitive effects and attenuation of learning and memory. The cellular mechanisms underlying the CNS effects of alcohol have yet to be fully elucidated and are likely to depend on the pattern and dose of alcohol exposure. Using electrophysiological recordings from hippocampal slices obtained from control and chronic alcohol-treated rats, we have investigated the effects of a binge pattern of alcohol abuse on synaptic plasticity in the CNS. The alcohol-treated animals were exposed to ethanol vapor for 12-14 days using an intermittent exposure paradigm (14 h ethanol exposure/10 h ethanol withdrawal daily; blood alcohol levels approximately 180 mg/dl), a paradigm that models human binge alcohol use. Induction of long-term potentiation (LTP) in the CA1 region of the hippocampus by tetanic stimulation of Schaffer collaterals was completely blocked in slices from the chronic alcohol-treated animals. LTP remained blocked 1 day after withdrawal of animals from alcohol, indicating that the neuroadaptive changes produced by alcohol were not readily reversible. Partial recovery was observed after withdrawal from alcohol for 5 days. Other measures of synaptic plasticity including posttetanic potentiation and paired-pulse facilitation were also altered by the intermittent alcohol treatment paradigm. The results suggest that alterations in synaptic plasticity induced by chronic intermittent ethanol consumption play an important role in the effects of binge alcohol use on learning and memory function.     

Intrastriatal dopamine D1 antagonism dampens neural plasticity in response to motor cortex lesion

Motor cortex lesions in rats partially denervate the striatum, producing behavioral deficits and inducing reactive neuroplasticity. Plastic responses include changes in growth-associated protein marker expression and anatomical restructuring. Corticostriatal plasticity is dependent on dopamine at the striatal target, where D1 receptor signaling reinforces behaviorally relevant neural activity. To determine whether striatal dopamine D1 receptor signaling is important for the growth-associated protein responses and behavioral recovery that follow unilateral motor cortex aspiration, the dopamine D1 receptor antagonist SCH23390 was intrastriatally infused in cortically lesioned animals. After a cortical aspiration lesion in Long Evans rats, the growth-associated proteins SCG10 and GAP-43 were upregulated in the cortex contralateral to the lesion at 30 days post-lesion. However, continuous unilateral intrastriatal infusion of SCH23390 prevented this aspiration-induced upregulation. Furthermore, lesioned rats demonstrated spontaneous sensorimotor improvement, in terms of limb-use symmetry, about 1 month post-lesion. This improvement was prevented with chronic intrastriatal SCH23390 infusion. The D1 receptor influence may be important to normalize corticostriatal activity (and observable behavior), either in a long-term manner or temporarily until other more permanent means of synaptic regulation, such as sprouting or synaptogenesis, may be implemented.     

Stress-facilitated LTD induces output plasticity through synchronized-spikes and spontaneous unitary discharges in the CA1 region of the hippocampus

Long-term potentiation (LTP) and long-term depression (LTD) of the excitatory synaptic inputs plasticity in the hippocampus is believed to underlie certain types of learning and memory. Especially, stressful experiences, well known to produce long-lasting strong memories of the event themselves, enable LTD by low frequency stimulation (LFS, 3 Hz) but block LTP induction by high frequency stimulation (HFS, 200 Hz). However, it is unknown whether stress-affected synaptic plasticity has an impact on the output plasticity. Thus, we have simultaneously studied the effects of stress on synaptic plasticity and neuronal output in the hippocampal CA1 region of anesthetized Wistar rats. Our results revealed that stress increased basal power spectrum of the evoked synchronized-spikes and enabled LTD induction by LFS. The induction of stress-facilitated LTD but not LFS induced persistent decreases of the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges; However, HFS induced LTP in non-stressed animals and increased the power spectrum of the synchronized-spikes, without affecting the frequency of the spontaneous unitary discharges, but HFS failed to induce LTP in stressed animals without affecting the power spectrum of the synchronized-spikes and the frequency of the spontaneous unitary discharges. These observations that stress-facilitated LTD induces the output plasticity through the synchronized-spikes and spontaneous unitary discharges suggest that these types of stress-related plasticity may play significant roles in distribution, amplification and integration of encoded information to other brain structures under stressful conditions.