Showing papers in "Nature Neuroscience in 2002"
TL;DR: This work shows that the optimal strategy in the face of uncertainty is to allow variability in redundant (task-irrelevant) dimensions, and proposes an alternative theory based on stochastic optimal feedback control, which emerges naturally from this framework.
Abstract: A central problem in motor control is understanding how the many biomechanical degrees of freedom are coordinated to achieve a common goal. An especially puzzling aspect of coordination is that behavioral goals are achieved reliably and repeatedly with movements rarely reproducible in their detail. Existing theoretical frameworks emphasize either goal achievement or the richness of motor variability, but fail to reconcile the two. Here we propose an alternative theory based on stochastic optimal feedback control. We show that the optimal strategy in the face of uncertainty is to allow variability in redundant (task-irrelevant) dimensions. This strategy does not enforce a desired trajectory, but uses feedback more intelligently, correcting only those deviations that interfere with task goals. From this framework, task-constrained variability, goal-directed corrections, motor synergies, controlled parameters, simplifying rules and discrete coordination modes emerge naturally. We present experimental results from a range of motor tasks to support this theory.
2,776 citations
TL;DR: It is reported that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival.
Abstract: Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene expression as strongly as did stimulation of L-type calcium channels. In contrast, calcium entry through extrasynaptic NMDA receptors, triggered by bath glutamate exposure or hypoxic/ischemic conditions, activated a general and dominant CREB shut-off pathway that blocked induction of BDNF expression. Synaptic NMDA receptors have anti-apoptotic activity, whereas stimulation of extrasynaptic NMDA receptors caused loss of mitochondrial membrane potential (an early marker for glutamate-induced neuronal damage) and cell death. Specific blockade of extrasynaptic NMDA receptors may effectively prevent neuron loss following stroke and other neuropathological conditions associated with glutamate toxicity.
1,590 citations
TL;DR: In monozygotic twins discordant for trauma exposure, it is found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology.
Abstract: In animals, exposure to severe stress can damage the hippocampus. Recent human studies show smaller hippocampal volume in individuals with the stress-related psychiatric condition posttraumatic stress disorder (PTSD). Does this represent the neurotoxic effect of trauma, or is smaller hippocampal volume a pre-existing condition that renders the brain more vulnerable to the development of pathological stress responses? In monozygotic twins discordant for trauma exposure, we found evidence that smaller hippocampi indeed constitute a risk factor for the development of stress-related psychopathology. Disorder severity in PTSD patients who were exposed to trauma was negatively correlated with the hippocampal volume of both the patients and the patients’ trauma-unexposed identical co-twin. Furthermore, severe PTSD twin pairs—both the trauma-exposed and unexposed members—had significantly smaller hippocampi than non-PTSD pairs.
1,469 citations
TL;DR: Three peptides were administered intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.
Abstract: Neuropeptides act as neuronal messengers in the brain, influencing many neurobehavioral functions1. Their experimental and therapeutic use in humans has been hampered because, when administered systemically, these compounds do not readily pass the blood–brain barrier, and they evoke potent hormone-like side effects when circulating in the blood2,3. We administered three peptides, melanocortin(4–10) (MSH/ACTH(4–10)), vasopressin and insulin, intranasally and found that they achieved direct access to the cerebrospinal fluid (CSF) within 30 minutes, bypassing the bloodstream.
1,259 citations
TL;DR: It is concluded that the CNS applies a specific neural mechanism to produce intentional binding of actions and their effects in conscious awareness.
Abstract: Humans have the conscious experience of 'free will': we feel we can generate our actions, and thus affect our environment. Here we used the perceived time of intentional actions and of their sensory consequences as a means to study consciousness of action. These perceived times were attracted together in conscious awareness, so that subjects perceived voluntary movements as occurring later and their sensory consequences as occurring earlier than they actually did. Comparable involuntary movements caused by magnetic brain stimulation reversed this attraction effect. We conclude that the CNS applies a specific neural mechanism to produce intentional binding of actions and their effects in conscious awareness.
1,168 citations
TL;DR: It is shown that lymphoblast mitochondria from patients with HD have a lower membrane potential and depolarize at lower calcium loads than do mitochondriaFrom controls, and mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle.
Abstract: Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats in the gene encoding huntingtin protein (Htt), but the mechanisms by which this mutant protein causes neurodegeneration remain unknown. Here we show that lymphoblast mitochondria from patients with HD have a lower membrane potential and depolarize at lower calcium loads than do mitochondria from controls. We found a similar defect in brain mitochondria from transgenic mice expressing full-length mutant huntingtin, and this defect preceded the onset of pathological or behavioral abnormalities by months. By electron microscopy, we identified N-terminal mutant huntingtin on neuronal mitochondrial membranes, and by incubating normal mitochondria with a fusion protein containing an abnormally long polyglutamine repeat, we reproduced the mitochondrial calcium defect seen in human patients and transgenic animals. Thus, mitochondrial calcium abnormalities occur early in HD pathogenesis and may be a direct effect of mutant huntingtin on the organelle.
1,023 citations
TL;DR: This article showed that passive immunization with this anti-Aβ monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and sequestration of a soluble brain Aβ species.
Abstract: We have previously shown that chronic treatment with the monoclonal antibody m266, which is specific for amyloid β-peptide (Aβ), increases plasma concentrations of Aβ and reduces Aβ burden in the PDAPP transgenic mouse model of Alzheimer's disease (AD). We now report that administration of m266 to PDAPP mice can rapidly reverse memory deficits in both an object recognition task and a holeboard learning and memory task, but without altering brain Aβ burden. We also found that an Aβ/antibody complex was present in both the plasma and the cerebrospinal fluid of m266-treated mice. Our data indicate that passive immunization with this anti-Aβ monoclonal antibody can very rapidly reverse memory impairment in certain learning and memory tasks in the PDAPP mouse model of AD, owing perhaps to enhanced peripheral clearance and (or) sequestration of a soluble brain Aβ species.
971 citations
TL;DR: A model of visual motion perception using standard estimation theory, under the assumptions that there is noise in the initial measurements and slower motions are more likely to occur than faster ones, is formulated and found that specific instantiation of such a velocity estimator can account for a wide variety of psychophysical phenomena.
Abstract: ing incorrect velocities. We show that these ‘illusions’ arise naturally in a system that attempts to estimate local image velocity. We formulated a model of visual motion perception using standard estimation theory, under the assumptions that (i) there is noise in the initial measurements and (ii) slower motions are more likely to occur than faster ones. We found that specific instantiation of such a velocity estimator can account for a wide variety of psychophysical phenomena.
959 citations
TL;DR: The findings extend a proposed model of social cognition by highlighting a functional dissociation between automatic engagement of amygdala versus intentional engagement of STS in social judgment.
Abstract: Successful social interaction partly depends on appraisal of others from their facial appearance. A critical aspect of this appraisal relates to whether we consider others to be trustworthy. We determined the neural basis for such trustworthiness judgments using event-related functional magnetic resonance imaging. Subjects viewed faces and assessed either trustworthiness or age. In a parametric factorial design, trustworthiness ratings were correlated with BOLD signal change to reveal task-independent increased activity in bilateral amygdala and right insula in response to faces judged untrustworthy. Right superior temporal sulcus (STS) showed enhanced signal change during explicit trustworthiness judgments alone. The findings extend a proposed model of social cognition by highlighting a functional dissociation between automatic engagement of amygdala versus intentional engagement of STS in social judgment.
955 citations
TL;DR: The temporal structure of local field potential activity and spiking from area LIP in two awake macaques during a memory-saccade task was studied and it was found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate.
Abstract: Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25-90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.
938 citations
TL;DR: Human ORs cover a similar 'receptor space' as the mouse ORs, suggesting that the human olfactory system has retained the ability to recognize a broad spectrum of chemicals even though humans have lost nearly two-thirds of the OR genes as compared to mice.
Abstract: Olfactory receptor (OR) genes are the largest gene superfamily in vertebrates. We have identified the mouse OR genes from the nearly complete Celera mouse genome by a comprehensive data mining strategy. We found 1,296 mouse OR genes (including ∼20% pseudogenes), which can be classified into 228 families. OR genes are distributed in 27 clusters on all mouse chromosomes except 12 and Y. One OR gene cluster matches a known locus mediating a specific anosmia, indicating the anosmia may be due directly to the loss of receptors. A large number of apparently functional 'fish-like' Class I OR genes in the mouse genome may have important roles in mammalian olfaction. Human ORs cover a similar 'receptor space' as the mouse ORs, suggesting that the human olfactory system has retained the ability to recognize a broad spectrum of chemicals even though humans have lost nearly two-thirds of the OR genes as compared to mice.
TL;DR: The authors found that activation of unmyelinated tactile (CT) afferents produced a faint sensation of pleasant touch, which may underlie emotional, hormonal and affiliative responses to skin-to-skin contact between individuals.
Abstract: There is dual tactile innervation of the human hairy skin: in addition to fast-conducting myelinated afferent fibers, there is a system of slow-conducting unmyelinated (C) afferents that respond to light touch. In a unique patient lacking large myelinated afferents, we found that activation of C tactile (CT) afferents produced a faint sensation of pleasant touch. Functional magnetic resonance imaging (fMRI) analysis during CT stimulation showed activation of the insular region, but not of somatosensory areas S1 and S2. These findings identify CT as a system for limbic touch that may underlie emotional, hormonal and affiliative responses to caress-like, skin-to-skin contact between individuals.
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TL;DR: This new approach promises to revolutionize pain diagnosis and management by developing treatments that specifically target underlying causes rather than just symptoms.
Abstract: Pain can be an adaptive sensation, an early warning to protect the body from tissue injury. By the introduction of hypersensitivity to normally innocuous stimuli, pain may also aid in repair after tissue damage. Pain can also be maladaptive, reflecting pathological function of the nervous system. Multiple molecular and cellular mechanisms operate alone and in combination within the peripheral and central nervous systems to produce the different forms of pain. Elucidation of these mechanisms is key to the development of treatments that specifically target underlying causes rather than just symptoms. This new approach promises to revolutionize pain diagnosis and management.
TL;DR: It is shown that hippocampal lesions produce a severe and selective impairment in the capacity of rats to remember the sequential ordering of a series of odors, despite an intact capacity to recognize odors that recently occurred.
Abstract: Recent models of hippocampal function emphasize the potential role of this brain structure in encoding and retrieving sequences of events that compose episodic memories. Here we show that hippocampal lesions produce a severe and selective impairment in the capacity of rats to remember the sequential ordering of a series of odors, despite an intact capacity to recognize odors that recently occurred. These findings support the hypothesis that hippocampal networks mediate associations between sequential events that constitute elements of an episodic memory.
TL;DR: A new role for endocannabinoids is demonstrated in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control.
Abstract: The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control.
TL;DR: It is reported that several basic auditory nerve fiber tuning properties can be accounted for by adapting a population of filter shapes to encode natural sounds efficiently.
Abstract: The auditory system encodes sound by decomposing the amplitude signal arriving at the ear into multiple frequency bands whose center frequencies and bandwidths are approximately exponential functions of the distance from the stapes. This organization is thought to result from the adaptation of cochlear mechanisms to the animal's auditory environment. Here we report that several basic auditory nerve fiber tuning properties can be accounted for by adapting a population of filter shapes to encode natural sounds efficiently. The form of the code depends on sound class, resembling a Fourier transformation when optimized for animal vocalizations and a wavelet transformation when optimized for non-biological environmental sounds. Only for the combined set does the optimal code follow scaling characteristics of physiological data. These results suggest that auditory nerve fibers encode a broad set of natural sounds in a manner consistent with information theoretic principles.
TL;DR: Progress in creating useful human BMIs is accelerating, and studies in behaving monkeys show that neural output from the motor cortex can be used to control computer cursors almost as effectively as a natural hand would carry out the task.
Abstract: Recent technological and scientific advances have generated wide interest in the possibility of creating a brain-machine interface (BMI), particularly as a means to aid paralyzed humans in communication. Advances have been made in detecting neural signals and translating them into command signals that can control devices. We now have systems that use externally derived neural signals as a command source, and faster and potentially more flexible systems that directly use intracortical recording are being tested. Studies in behaving monkeys show that neural output from the motor cortex can be used to control computer cursors almost as effectively as a natural hand would carry out the task. Additional research findings explore the possibility of using computers to return behaviorally useful feedback information to the cortex. Although significant scientific and technological challenges remain, progress in creating useful human BMIs is accelerating.
TL;DR: An important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells is demonstrated and retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro.
Abstract: Radial glial cells, ubiquitous throughout the developing CNS, guide radially migrating neurons and are the precursors of astrocytes. Recent evidence indicates that radial glial cells also generate neurons in the developing cerebral cortex. Here we investigated the role of the transcription factor Pax6 expressed in cortical radial glia. We showed that radial glial cells isolated from the cortex of Pax6 mutant mice have a reduced neurogenic potential, whereas the neurogenic potential of non-radial glial precursors is not affected. Consistent with defects in only one neurogenic lineage, the number of neurons in the Pax6 mutant cortex in vivo is reduced by half. Conversely, retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro. These results demonstrated an important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells.
TL;DR: Brain activity during attention shifts using rapid, event-related fMRI of human observers as they covertly shifted attention between two peripheral spatial locations suggests that activation of the parietal cortex is associated with a discrete signal to shift spatial attention, and is not the source of a signal to continuously maintain the current attentive state.
Abstract: Observers viewing a complex visual scene selectively attend to relevant locations or objects and ignore irrelevant ones. Selective attention to an object enhances its neural representation in extrastriate cortex, compared with those of unattended objects, via top-down attentional control signals. The posterior parietal cortex is centrally involved in this control of spatial attention. We examined brain activity during attention shifts using rapid, event-related fMRI of human observers as they covertly shifted attention between two peripheral spatial locations. Activation in extrastriate cortex increased after a shift of attention to the contralateral visual field and remained high during sustained contralateral attention. The time course of activity was substantially different in posterior parietal cortex, where transient increases in activation accompanied shifts of attention in either direction. This result suggests that activation of the parietal cortex is associated with a discrete signal to shift spatial attention, and is not the source of a signal to continuously maintain the current attentive state.
TL;DR: Insulin receptors in discrete areas of the hypothalamus have a physiological role in the control of food intake, fat mass and hepatic action of insulin.
Abstract: We investigated the role of hypothalamic insulin signaling in the regulation of energy balance and insulin action in rats through selective decreases in insulin receptor expression in discrete hypothalamic nuclei. We generated an antisense oligodeoxynucleotide directed against the insulin receptor precursor protein and administered this directly into the third cerebral ventricle. Immunostaining of rat brains after 7-day administration of the oligodeoxynucleotide showed a selective decrease of insulin receptor protein within cells in the medial portion of the arcuate nucleus (decreased by ∼80% as compared to rats treated with a control oligodeoxynucleotide). Insulin receptors in other hypothalamic and extra-hypothalamic areas were not affected. This selective decrease in hypothalamic insulin receptor protein was accompanied by rapid onset of hyperphagia and increased fat mass. During insulin-clamp studies, physiological hyperinsulinemia decreased glucose production by 55% in rats treated with control oligodeoxynucleotides but by only 25% in rats treated with insulin receptor antisense oligodeoxynucleotides. Thus, insulin receptors in discrete areas of the hypothalamus have a physiological role in the control of food intake, fat mass and hepatic action of insulin.
TL;DR: Findings indicate that TRPV1 participates in normal bladder function and is essential for normal mechanically evoked purinergic signaling by the urothelium.
Abstract: In the urinary bladder, the capsaicin-gated ion channel TRPV1 is expressed both within afferent nerve terminals and within the epithelial cells that line the bladder lumen. To determine the significance of this expression pattern, we analyzed bladder function in mice lacking TRPV1. Compared with wild-type littermates, trpv1(-/-) mice had a higher frequency of low-amplitude, non-voiding bladder contractions. This alteration was accompanied by reductions in both spinal cord signaling and reflex voiding during bladder filling (under anesthesia). In vitro, stretch-evoked ATP release and membrane capacitance changes were diminished in bladders excised from trpv1(-/-) mice, as was hypoosmolality-evoked ATP release from cultured trpv1(-/-) urothelial cells. These findings indicate that TRPV1 participates in normal bladder function and is essential for normal mechanically evoked purinergic signaling by the urothelium.
TL;DR: This article used magnetoencephalography (MEG) to investigate stages of processing in face perception in humans and found that face processing proceeds through two stages: an initial stage of face categorization, and a later stage at which the identity of the individual face is extracted.
Abstract: Here we used magnetoencephalography (MEG) to investigate stages of processing in face perception in humans. We found a face-selective MEG response occurring only 100 ms after stimulus onset (the 'M100'), 70 ms earlier than previously reported. Further, the amplitude of this M100 response was correlated with successful categorization of stimuli as faces, but not with successful recognition of individual faces, whereas the previously-described face-selective 'M170' response was correlated with both processes. These data suggest that face processing proceeds through two stages: an initial stage of face categorization, and a later stage at which the identity of the individual face is extracted.
TL;DR: Progeny of adult rat neural stem cells, when co-cultured with primary neurons and astrocytes from neonatal hippocampus, develop into electrically active neurons and integrate into neuronal networks with functional synaptic transmission.
Abstract: Neural stem cells are present both in the developing nervous system and in the adult nervous system of all mammals, including humans. Little is known, however, about the extent to which stem cells in adults can give rise to new neurons. We used immunocytochemistry, electron microscopy, fluorescence microscopy (FM imaging) and electrophysiology to demonstrate that progeny of adult rat neural stem cells, when co-cultured with primary neurons and astrocytes from neonatal hippocampus, develop into electrically active neurons and integrate into neuronal networks with functional synaptic transmission. We also found that functional neurogenesis from adult stem cells is possible in co-culture with astrocytes from neonatal and adult hippocampus. These studies show that neural stem cells derived from adult tissues, like those derived from embryonic tissues, retain the potential to differentiate into functional neurons with essential properties of mature CNS neurons.
TL;DR: Results indicate that both the morphology and neurophysiology of Heschl's gyrus have an essential impact on musical aptitude.
Abstract: Using magnetoencephalography (MEG), we compared the processing of sinusoidal tones in the auditory cortex of 12 non-musicians, 12 professional musicians and 13 amateur musicians. We found neurophysiological and anatomical differences between groups. In professional musicians as compared to non-musicians, the activity evoked in primary auditory cortex 19–30 ms after stimulus onset was 102% larger, and the gray matter volume of the anteromedial portion of Heschl's gyrus was 130% larger. Both quantities were highly correlated with musical aptitude, as measured by psychometric evaluation. These results indicate that both the morphology and neurophysiology of Heschl's gyrus have an essential impact on musical aptitude.
TL;DR: It is shown that intermediate complexity (IC) features are optimal for the basic visual task of classification and suggest a specific role for IC features in visual processing and a principle for their extraction.
Abstract: The human visual system analyzes shapes and objects in a series of stages in which stimulus features of increasing complexity are extracted and analyzed. The first stages use simple local features, and the image is subsequently represented in terms of larger and more complex features. These include features of intermediate complexity and partial object views. The nature and use of these higher-order representations remains an open question in the study of visual processing by the primate cortex. Here we show that intermediate complexity (IC) features are optimal for the basic visual task of classification. Moderately complex features are more informative for classification than very simple or very complex ones, and so they emerge naturally by the simple coding principle of information maximization with respect to a class of images. Our findings suggest a specific role for IC features in visual processing and a principle for their extraction.
TL;DR: It is found that attention modulated neural activity in the human lateral geniculate nucleus (LGN) in several ways: it enhanced neural responses to attended stimuli, attenuated responses to ignored stimuli and increased baselineActivity in the absence of visual stimulation.
Abstract: Attentional mechanisms are important for selecting relevant information and filtering out irrelevant information from cluttered visual scenes. Selective attention has previously been shown to affect neural activity in both extrastriate and striate visual cortex. Here, evidence from functional brain imaging shows that attentional response modulation is not confined to cortical processing, but can occur as early as the thalamic level. We found that attention modulated neural activity in the human lateral geniculate nucleus (LGN) in several ways: it enhanced neural responses to attended stimuli, attenuated responses to ignored stimuli and increased baseline activity in the absence of visual stimulation. The LGN, traditionally viewed as the gateway to visual cortex, may also serve as a 'gatekeeper' in controlling attentional response gain.
TL;DR: The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
Abstract: Both dopaminergic neurotransmission and prefrontal cortex (PFC) function are known to be abnormal in schizophrenia. To test the hypothesis that these phenomena are related, we measured presynaptic dopaminergic function simultaneously with regional cerebral blood flow during the Wisconsin Card Sorting Test (WCST) and a control task in unmedicated schizophrenic subjects and matched controls. We show that the dopaminergic uptake constant Ki in the striatum was significantly higher for patients than for controls. Patients had significantly less WCST-related activation in PFC. The two parameters were strongly linked in patients, but not controls. The tight within-patient coupling of these values, with decreased PFC activation predicting exaggerated striatal 6-fluorodopa uptake, supports the hypothesis that prefrontal cortex dysfunction may lead to dopaminergic transmission abnormalities.
TL;DR: It is found that CREB is crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories.
Abstract: The cAMP-responsive element binding protein (CREB) family of transcription factors is thought to be critical in memory formation. To define the role of CREB in distinct memory processes, we derived transgenic mice with an inducible and reversible CREB repressor by fusing CREBS133A to a tamoxifen (TAM)-dependent mutant of an estrogen receptor ligand-binding domain (LBD). We found that CREB is crucial for the consolidation of long-term conditioned fear memories, but not for encoding, storage or retrieval of these memories. Our studies also showed that CREB is required for the stability of reactivated or retrieved conditioned fear memories. Although the transcriptional processes necessary for the stability of initial and reactivated memories differ, CREB is required for both. The findings presented here delineate the memory processes that require CREB and demonstrate the power of LBD-inducible transgenic systems in the study of complex cognitive processes.
TL;DR: PET imaging data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.
Abstract: Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.
TL;DR: The data indicate that mEPSC amplitudes can be globally scaled up or down as a function of development and sensory experience, and suggest that synaptic scaling may be involved in the activity-dependent refinement of cortical connectivity.
Abstract: The mechanisms underlying experience-dependent plasticity and refinement of central circuits are not yet fully understood. A non-Hebbian form of synaptic plasticity, which scales synaptic strengths up or down to stabilize firing rates, has recently been discovered in cultured neuronal networks. Here we demonstrate the existence of a similar mechanism in the intact rodent visual cortex. The frequency of miniature excitatory postsynaptic currents (mEPSCs) in principal neurons increased steeply between post-natal days 12 and 23. There was a concomitant decrease in mEPSC amplitude, which was prevented by rearing rats in complete darkness from 12 days of age. In addition, as little as two days of monocular deprivation scaled up mEPSC amplitude in a layer- and age-dependent manner. These data indicate that mEPSC amplitudes can be globally scaled up or down as a function of development and sensory experience, and suggest that synaptic scaling may be involved in the activity-dependent refinement of cortical connectivity.