Transfer of learning after updating training mediated by the striatum

Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.     

Selective D2 receptor actions on the functional circuitry of working memory

Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2 receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process.     

Dichotomous dopaminergic control of striatal synaptic plasticity

At synapses between cortical pyramidal neurons and principal striatal medium spiny neurons (MSNs), postsynaptic D1 and D2 dopamine (DA) receptors are postulated to be necessary for the induction of long-term potentiation and depression, respectively-forms of plasticity thought to underlie associative learning. Because these receptors are restricted to two distinct MSN populations, this postulate demands that synaptic plasticity be unidirectional in each cell type. Using brain slices from DA receptor transgenic mice, we show that this is not the case. Rather, DA plays complementary roles in these two types of MSN to ensure that synaptic plasticity is bidirectional and Hebbian. In models of Parkinson's disease, this system is thrown out of balance, leading to unidirectional changes in plasticity that could underlie network pathology and symptoms.     

Building neural representations of habits

Memories for habits and skills ("implicit or procedural memory") and memories for facts ("explicit or episodic memory") are built up in different brain systems and are vulnerable to different neurodegenerative disorders in humans. So that the striatum-based mechanisms underlying habit formation could be studied, chronic recordings from ensembles of striatal neurons were made with multiple tetrodes as rats learned a T-maze procedural task. Large and widely distributed changes in the neuronal activity patterns occurred in the sensorimotor striatum during behavioral acquisition, culminating in task-related activity emphasizing the beginning and end of the automatized procedure. The new ensemble patterns remained stable during weeks of subsequent performance of the same task. These results suggest that the encoding of action in the sensorimotor striatum undergoes dynamic reorganization as habit learning proceeds.     

Cloning and expression of a cocaine-sensitive dopamine transporter complementary DNA

A rat dopamine (DA) transporter complementary DNA has been isolated with combined complementary DNA homology and expression approaches. The DA transporter is a 619-amino acid protein with 12 hydrophobic putative membrane-spanning domains and homology to the norepinephrine and gamma-aminobutyric acid transporters. The expressed complementary DNA confers transport of [3H]DA in Xenopus oocytes and in COS cells. Binding of the cocaine analog [3H]CFT ([3H]2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane) to transfected COS cell membranes yields a pharmacological profile similar to that in striatal membranes.     

Nucleus accumbens D2/3 receptors predict trait impulsivity and cocaine reinforcement

Stimulant addiction is often linked to excessive risk taking, sensation seeking, and impulsivity, but in ways that are poorly understood. We report here that a form of impulsivity in rats predicts high rates of intravenous cocaine self-administration and is associated with changes in dopamine (DA) function before drug exposure. Using positron emission tomography, we demonstrated that D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rats that were never exposed to cocaine and that such effects are independent of DA release. These data demonstrate that trait impulsivity predicts cocaine reinforcement and that D2 receptor dysfunction in abstinent cocaine addicts may, in part, be determined by premorbid influences.     

Reversal of antipsychotic-induced working memory deficits by short-term dopamine D1 receptor stimulation

Chronic blockade of dopamine D2 receptors, a common mechanism of action for antipsychotic drugs, down-regulates D1 receptors in the prefrontal cortex and, as shown here, produces severe impairments in working memory. These deficits were reversed in monkeys by short-term coadministration of a D1 agonist, ABT 431, and this improvement was sustained for more than a year after cessation of D1 treatment. These findings indicate that pharmacological modulation of the D1 signaling pathway can produce long-lasting changes in functional circuits underlying working memory. Resetting this pathway by brief exposure to the agonist may provide a valuable strategy for therapeutic intervention in schizophrenia and other dopamine dysfunctional states.     

People with absolute pitch process tones without producing a p300

The P300 is a positive-going component of the event-related potential. In subjects with absolute, or "perfect," pitch, the P300 elicited by the less frequent of two auditory probes is small or absent. In these subjects, visual probes elicit a normal P300. These results support the view of P300 as a manifestation of the updating of working memory.     

铅对旱地红壤脱氢酶活性的影响

通过实验室培养试验研究外源添加单一重金属铅(Pb)在不同浓度和培养时间下对旱地红壤脱氢酶活性的影响。结果表明,在旱地红壤中,当Pb浓度低于200 mg/kg土时,脱氢酶活性随浓度的增加而上升,在100 mg/kg土时活性最大;当Pb浓度大于200mg/kg土时,其活性随着Pb浓度的升高而逐渐降低,且浓度越高对脱氢酶活性的抑制作用愈显著。即200 mg/kg土可作为Pb对脱氢酶活性影响的临界浓度。此外,脱氢酶活性随培养时间的变化而呈现类似的变化,在培养10 d以前为促进作用,以后随培养时间的推移而日渐受到抑制,第10天可为脱氢酶活性受Pb胁迫的临界期。     

Awake hippocampal sharp-wave ripples support spatial memory

The hippocampus is critical for spatial learning and memory. Hippocampal neurons in awake animals exhibit place field activity that encodes current location, as well as sharp-wave ripple (SWR) activity during which representations based on past experiences are often replayed. The relationship between these patterns of activity and the memory functions of the hippocampus is poorly understood. We interrupted awake SWRs in animals learning a spatial alternation task. We observed a specific learning and performance deficit that persisted throughout training. This deficit was associated with awake SWR activity, as SWR interruption left place field activity and post-experience SWR reactivation intact. These results provide a link between awake SWRs and hippocampal memory processes, which suggests that awake replay of memory-related information during SWRs supports learning and memory-guided decision-making.     

Flexible control of mutual inhibition: a neural model of two-interval discrimination

Networks adapt to environmental demands by switching between distinct dynamical behaviors. The activity of frontal-lobe neurons during two-interval discrimination tasks is an example of these adaptable dynamics. Subjects first perceive a stimulus, then hold it in working memory, and finally make a decision by comparing it with a second stimulus. We present a simple mutual-inhibition network model that captures all three task phases within a single framework. The model integrates both working memory and decision making because its dynamical properties are easily controlled without changing its connectivity. Mutual inhibition between nonlinear units is a useful design motif for networks that must display multiple behaviors.     

The role of working memory in visual selective attention

The hypothesis that working memory is crucial for reducing distraction by maintaining the prioritization of relevant information was tested in neuroimaging and psychological experiments with humans. Participants performed a selective attention task that required them to ignore distractor faces while holding in working memory a sequence of digits that were in the same order (low memory load) or a different order (high memory load) on every trial. Higher memory load, associated with increased prefrontal activity, resulted in greater interference effects on behavioral performance from the distractor faces, plus increased face-related activity in the visual cortex. These findings confirm a major role for working memory in the control of visual selective attention.     

Synaptic theory of working memory

It is usually assumed that enhanced spiking activity in the form of persistent reverberation for several seconds is the neural correlate of working memory. Here, we propose that working memory is sustained by calcium-mediated synaptic facilitation in the recurrent connections of neocortical networks. In this account, the presynaptic residual calcium is used as a buffer that is loaded, refreshed, and read out by spiking activity. Because of the long time constants of calcium kinetics, the refresh rate can be low, resulting in a mechanism that is metabolically efficient and robust. The duration and stability of working memory can be regulated by modulating the spontaneous activity in the network.     

身体活动的心理健康效应：效果与机制*

身体活动在个体发展各阶段具有广泛的心理健康效应。已有研究提示，有氧练习与抗阻练习对儿童、青少年的P3与工作记忆等认知表现具有积极影响，并且对学业成就测试有潜在积极效益。身体活动还对成年群体的执行功能及抑郁表现具有中等程度的改善效应，并且对罹患阿尔茨海默症及多发性硬化症老年群体的认知功能具有积极临床效果。身体活动心理效益的生物学机制主要体现在血液灌注水平提升、突触发生及脑源性营养因子的表达。未来研究中，应当丰富随机对照与纵向性质研究，身体活动与其它因素对脑功能影响的交互作用机制需要进一步了解。     

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory

The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.     

Erratum

In the report "Prenatal exposure to carbon monoxide: Learning and memory deficits" by C. F. Mactutus and L. D. Fechter (27 Jan., p. 409), the second sentence of the second full paragraph in column 3 of page 410 should have read, "A 2 by 2 analysis of covariance on the number of avoidance responses with covariates of number of avoidance responses in acquisition and number of adaptation and intertrial responses during reacquisition revealed significant effects of training contingency [F( 1, 57) = 23.8, P < 0.001] and an interaction of CO exposure with training contingency [F(1, 57) = 7.6, P < 0.008].     

Actinomycin D blocks formation of memory of shock-avoidance in goldfish

When 2 micrograms of antinomycin D was injected intracranially into goldfish immediately after a training session, the formation of long-term memory of a shock-avoidance was blocked. The results are discussed in relation to similar findings with acetoxycycloheximide and puromycin in the goldfish and with apparently conflicting results in the mouse.     

Cholinergic enhancement and increased selectivity of perceptual processing during working memory

Using functional magnetic resonance imaging, we investigated the mechanism by which cholinergic enhancement improves working memory. We studied the effect of the cholinesterase inhibitor physostigmine on subcomponents of this complex function. Cholinergic enhancement increased the selectivity of neural responses in extrastriate cortices during visual working memory, particularly during encoding. It also increased the participation of ventral extrastriate cortex during memory maintenance and decreased the participation of anterior prefrontal cortex. These results indicate that cholinergic enhancement improves memory performance by augmenting the selectivity of perceptual processing during encoding, thereby simplifying processing demands during memory maintenance and reducing the need for prefrontal participation.     

采用双任务范式使被试将工作记忆信息保存在工作记忆当中并完成选择性注意任务,结果发现:视觉空间工作记忆负荷不能使熟悉面孔的干扰效应消失,语义工作记忆负荷使熟悉面孔的干扰效应在高知觉负荷条件下消失.因此,熟悉面孔在高知觉负荷条件下可能是以语义的方式存储在工作记忆当中,在低知觉负荷条件下可能是同时存储在视觉空间工作记忆和语义工作记忆中.

采用双任务范式使被试将工作记忆信息保存在工作记忆当中并完成选择性注意任务,结果发现:视觉空间工作记忆负荷不能使熟悉面孔的干扰效应消失,语义工作记忆负荷使熟悉面孔的干扰效应在高知觉负荷条件下消失.因此,熟悉面孔在高知觉负荷条件下可能是以语义的方式存储在工作记忆当中,在低知觉负荷条件下可能是同时存储在视觉空间工作记忆和语义工作记忆中.     

Spontaneous changes of neocortical code for associative memory during consolidation

After learning, the medial prefrontal cortex (mPFC) gradually comes to modulate the expression of memories that initially depended on the hippocampus. We show that during this consolidation period, neural firing in the mPFC becomes selective for the acquired memories. After acquisition of memory associations, neuron populations in the mPFC of rats developed sustained activity during the interval between two paired stimuli, but reduced activity during the corresponding interval between two unpaired stimuli. These new patterns developed over a period of several weeks after learning, with and without continued conditioning trials. Thus, in agreement with a central tenet of consolidation theory, acquired associations initiate subsequent, gradual processes that result in lasting changes of the mPFC's code, without continued training.