Higher-order associative processing in Hermissenda suggests multiple sites of neuronal modulation. (17/1661)

Two important features of modern accounts of associative learning are (1) the capacity for contextual stimuli to serve as a signal for an unconditioned stimulus (US) and (2) the capacity for a previously conditioned (excitatory) stimulus to "block" learning about a redundant stimulus when both stimuli serve as a signal for the same US. Here, we examined the process of blocking, thought by some to reflect a cognitive aspect of classical conditioning, and its underlying mechanisms in the marine mollusc Hermissenda. In two behavioral experiments, a context defined by chemosensory stimuli was made excitatory by presenting unsignalled USs (rotation) in that context. The excitatory context subsequently blocked overt learning about a discrete conditioned stimulus (CS; light) paired with the US in that context. In a third experiment, the excitability of the B photoreceptors in the Hermissenda eye, which typically increases following light-rotation pairings, was examined in behaviorally blocked animals, as well as in animals that had acquired a normal CS-US association or animals that had been exposed to the CS and US unpaired. Both the behaviorally blocked and the "normal" learning groups exhibited increases in neuronal excitability relative to unpaired animals. However, light-induced multiunit activity in pedal nerves was suppressed following normal conditioning but not in blocked or unpaired control animals, suggesting that the expression of blocking is mediated by neuronal modifications not directly reflected in B-cell excitability, possibly within an extensive network of central light-responsive interneurons.  (+info)

Neuronal tuning and associative mechanisms in form representation. (18/1661)

We examine the hypothesis that the form representation in the anterior inferotemporal (AIT) cortex is acquired through learning. According to this hypothesis, perceptual aspects of the temporal association area are closely related to its visual representation, in that the response selectivity of AIT neurons can be influenced by visual experience. On the basis of the neurophysiological evidence, we summarize two neuronal mechanisms that subserve the acquisition of form selectivity in AIT neurons. The first mechanism is neuronal tuning to particular stimuli that were learned in a cognitive task. The second mechanism is association, with which relevant information can be retrieved from other stored memories. On the grounds that long-term memory of objects is acquired and organized by at least these two neuronal mechanisms in the temporal association area, we further present a model of the cognitive memory system that unifies perception and imagery.  (+info)

The role of dendritic filtering in associative long-term synaptic plasticity. (19/1661)

Several forms of synaptic plasticity in the neocortex and hippocampus depend on the temporal coincidence of presynaptic activity and postsynaptic trains of action potentials (APs). This requirement is consistent with the Hebbian, or correlational, type of cellular learning rule used in many studies of associative synaptic plasticity. Recent experimental evidence suggests that APs initiated in the axosomatic area are actively back-propagated to the dendritic arborization of neocortical and pyramidal cells. High-frequency trains of postsynaptic APs that are used as conditioning stimuli for the induction of Hebbian-like plasticity in both neocortical and hippocampal pyramidal cells display attenuation of the dendritic AP amplitude during the train. This attenuation has been shown to be modulated by neurotransmitters and by electrical activity. We suggest here that both spike train attenuation in the dendrite and its modulation by neurotransmitters and electrical activity may have important functional consequences on the magnitude and/or the sign of the synaptic plasticity induced by a Hebbian pairing procedure.  (+info)

Responses of macaque perirhinal neurons during and after visual stimulus association learning. (20/1661)

Recent lesion studies have implicated the perirhinal cortex in learning that two objects are associated, i.e., visual association learning. In this experiment we tested whether neuronal responses to associated stimuli in perirhinal cortex are altered over the course of learning. Neurons were recorded from monkeys during performance of a visual discrimination task in which a predictor stimulus was followed, after a delay, by a GO or NO-GO choice stimulus. Association learning had two major influences on neuronal responses. First, responses to frequently paired predictor-choice stimuli were more similar to one another than was the case with infrequently paired stimuli. Second, the magnitude of activity during the delay was correlated with the magnitude of responses to both the predictor and choice stimuli. Both of these learning effects were found only for stimulus pairs that had been associated on at least 2 d of training. Early in training, the delay activity was correlated only with the response to the predictor stimuli. Thus, with long-term training, perirhinal neurons tend to link the representations of temporally associated stimuli.  (+info)

Testing for symmetry in the conditional discriminations of language-trained chimpanzees. (21/1661)

If subjects are taught to match Stimulus A to B and then, without further training, match B to A, they have passed a test of symmetry. It has been suggested that non-humans' lack of success on symmetry tests might be overcome by giving them a history of symmetry exemplar training, that is, by directly teaching a large number of conditional relations (e.g., AB, CD, EF,...) and also directly training the "reverse" of these relations (e.g., BA, DC, FE,...). The chimpanzee subjects of the present study, Sherman, Austin, and Lana, had already received extensive symmetry exemplar training as a result of attempts to teach a selection-based language system of lexigrams. The present study systematically subjected 2 of these chimps (Sherman and Lana), for the first time, to standard symmetry tests in controlled conditions. Both chimps failed the tests, even when their correct responses on test trials were reinforced. The findings do not support the exemplar training hypothesis, and cast doubt upon whether the chimps can pass tests of stimulus equivalence.  (+info)

Modulation of presynaptic action potential kinetics underlies synaptic facilitation of type B photoreceptors after associative conditioning in Hermissenda. (22/1661)

Descriptions of conditioned response generation in Hermissenda stipulate that the synaptic interaction between type B and A photoreceptors should be enhanced after associative pairings of light and rotation. Although evidence from several laboratories has confirmed this assumption, the mechanism underlying this synaptic facilitation has not been elucidated. Here we report that in vitro conditioning (i.e., light paired with stimulation of vestibular hair cells) modifies the kinetics of presynaptic action potentials in the B photoreceptor in a manner sufficient to account for this synaptic facilitation. After paired training, we observed an increase in the duration of evoked action potentials and a decrease in the amplitude of the spike afterhyperpolarization in the B-cell. As previously reported, paired training also enhanced the excitability (i.e., input resistance and evoked spike rate) of the B photoreceptor. In a second experiment, simultaneous recordings were made in type B and A photoreceptors, and paired training was found to produce an increase in the amplitude of the IPSP in the A photoreceptor in response to an evoked spike in the B-cell. Importantly, there was no change in the initial slope of the postsynaptic IPSP in the A photoreceptor, suggesting that spike duration-independent mechanisms of neurotransmitter exocytosis or postsynaptic receptor sensitivity did not contribute to the observed synaptic facilitation. Perfusion of 4-aminopyridine (4-AP) mimicked a known effect of behavioral conditioning in that it specifically reduced the amplitude of the transient voltage-dependent K(+) current (I(A)) in the B-cell, but in addition, produced action potential broadening and synaptic facilitation that was analogous to that observed after in vitro conditioning. Finally, the effect of 4-AP on B-cell action potentials and on the postsynaptic IPSP in the A-cell was occluded by previous paired (but not unpaired) training, suggesting that the prolongation of the B-cell action potential by a reduction of I(A) was sufficient to account for the observed synaptic facilitation. The occlusion of the effects of 4-AP by paired training was not attributable to a saturation of the capacity of the B-cell for transmitter exocytosis, because it was observed that tetraethylammonium (TEA)-induced inhibition of the delayed voltage-dependent K(+) current induced both spike broadening and synaptic facilitation regardless of training history. Collectively, these results demonstrate that training-induced facilitation at B-cell synapses is attributable to the effects of a reduction of a presynaptic K(+) conductance on action potential kinetics and suggest another critical similarity between the cellular basis for learning in Hermissenda and other invertebrate systems.  (+info)

Induction of plasticity in the human motor cortex by paired associative stimulation. (23/1661)

Current models of motor cortical plasticity, developed in studies on experimental animals, emphasize the importance of the conjoint activity of somatosensory afferents and intrinsic motor cortical circuits. The hypothesis that an enduring change in excitability in the cortical output circuitry can be induced in the human motor cortex by a paired-stimulation protocol was tested. Low-frequency median nerve stimulation was paired with transcranial magnetic stimulation (TMS) over the optimal cranial site for stimulating the abductor pollicis brevis muscle (APB). This protocol induced an increase in the amplitudes of the motor evoked potentials (MEPs) in the resting APB as well as a prolongation of the silent period measured in the precontracted APB following TMS; amplitudes of MEPs measured in voluntary contraction remained unchanged. Experiments testing the excitability of spinal motoneurons using F-wave studies and electrical stimulation of the brainstem suggested that the site of the plastic changes was within the motor cortex. The increases in resting amplitudes and silent period duration were conditionally dependent on the timing between the afferent and the magnetic stimulation in that they were present when events elicited by afferent and magnetic stimulation were synchronous at the level of the motor cortex. Plasticity induced by paired stimulation evolved rapidly (within 30 min), was persistent (minimum duration 30-60 min) yet reversible, and was topographically specific. This combination of features and the similarity to properties of induced enduring changes in synaptic efficacy, as elucidated in animal studies, leads us to propose that the induced plasticity may represent a signature of associative long-term potentiation of cortical synapses or closely related neuronal mechanisms in the human cortex.  (+info)

Modest neuropsychological deficits caused by reduced noradrenaline metabolism in mice heterozygous for a mutated tyrosine hydroxylase gene. (24/1661)

Tyrosine hydroxylase (TH) is the initial and rate-limiting enzyme for the biosynthesis of catecholamines that are considered to be involved in a variety of neuropsychiatric functions. Here, we report behavioral and neuropsychological deficits in mice carrying a single mutated allele of the TH gene in which TH activity in tissues is reduced to approximately 40% of the wild-type activity. In the mice heterozygous for the TH mutation, noradrenaline accumulation in brain regions was moderately decreased to 73-80% of the wild-type value. Measurement of extracellular noradrenaline level in the frontal cortex by the microdialysis technique showed a reduction in high K(+)-evoked noradrenaline release in the mutants. The mutant mice displayed impairment in the water-finding task associated with latent learning performance. They also exhibited mild impairment in long-term memory formation in three distinct forms of associative learning, including active avoidance, cued fear conditioning, and conditioned taste aversion. These deficits were restored by the drug-induced stimulation of noradrenergic activity. In contrast, the spatial learning and hippocampal long-term potentiation were normal in the mutants. These results provide genetic evidence that the central noradrenaline system plays an important role in memory formation, particularly in the long-term memory of conditioned learning.  (+info)