Long-term synaptic potentiation

Long-term synaptic potentiation (LTP) is a leading candidate for a synaptic mechanism of rapid learning in mammals. LTP is a persistent increase in synaptic efficacy that can be quickly induced. The biophysical process that controls one type of LTP is formally similar to a synaptic memory mechanism postulated decades ago by the psychologist Donald Hebb. A key aspect of the modification process involves the N-methyl-D-aspartate (NMDA) receptor-ionophore complex. This ionophore allows calcium influx only if the endogenous ligand glutamate binds to the NMDA receptor and if the voltage across the associated channel is also sufficiently depolarized to relieve a magnesium block. According to one popular hypothesis, the resulting increase in the intracellular calcium concentration activates protein kinases that enhance the postsynaptic conductance. Further biophysical and molecular understanding of the modification process should facilitate detailed explorations of the mnemonic functions of LTP.     

Long-term synaptic potentiation in the superior cervical ganglion

Brief tetanic stimulation of the preganglionic nerves to the superior cervical ganglion enhances the postganglionic response to single preganglionic stimuli for 1 to 3 hours. This long-term potentiation of transmission through the ganglion is apparently not attributable to a persistent muscarinic action of the preganglionic neurotransmitter, acetylcholine, since neither the magnitude nor the time course of the phenomenon is reduced by atropine. The decay of long-term potentiation can be described by a first-order kinetic process with a mean time constant of 80 minutes. We conclude that long-term potentiation, once considered a unique property of the hippocampus, is in fact a more general feature of synaptic function. This form of synaptic memory may significantly influence information processing and control in other regions of the nervous system, including autonomic ganglia.     

Neuronal correlates of goal-based motor selection in the prefrontal cortex

Choosing an action that leads to a desired goal requires an understanding of the linkages between actions and their outcomes. We investigated neural mechanisms of such goal-based action selection. We trained monkeys on a task in which the relation between visual cues, action types, and reward conditions changed regularly, such that the monkeys selected their actions based on anticipated reward conditions. A significant number of neurons in the medial prefrontal cortex were activated, after cue presentation and before motor execution, only by particular action-reward combinations. This prefrontal activity is likely to underlie goal-based action selection.     

Long-term potentiation in dentate gyrus: induction by asynchronous volleys in separate afferents

Long-term potentiation (LTP), a long-lasting enhancement of synaptic efficacy, is considered a model for learning and memory. In anesthetized rats, activation of dentate granule cells by stimulating either the medial or lateral perforant pathway at frequencies of 100 to 400 Hz produced LTP of the stimulated pathway preferentially at 400 Hz. However, hippocampal pathways do not normally fire at this high rate. Stimuli at 200 Hz were then applied to either the medial or lateral pathway separately, to both pathways simultaneously, or to the two pathways asynchronously so that the composite stimulus applied to the granule cell dendrite was 400 Hz. LTP was produced preferentially in the asynchronous condition. Thus, lower frequency, physiological input volleys arriving asynchronously at medial and lateral synapses can induce LTP by activating a 400-Hz sensitive mechanism capable of integrating spatially separated granule cell inputs. This may reflect how LTP is normally produced in the dentate gyrus.     

Conversion of working memory to motor sequence in the monkey premotor cortex

To plan a serial order behavior, we hold serial sensory information in our minds and convert it to a movement program. We trained monkeys to memorize a sequence of positional cues and to reproduce it by making saccades in either the original or reverse order. The order was determined in the middle of a trial on the basis of an instruction stimulus. Triggered by the instruction stimulus, single neurons in the dorsal premotor cortex became transiently active only when the order needed to be determined. These transient neurons, together with nearby sustained neurons that hold information on cue or movement sequences, appear to mediate the generation of a motor program from the maintained information.     

Unit responses to moving visual stimuli in the motor cortex of the cat

Neurons in the pericruciate cortex of the cat were tested with moving visual stimuli for responses to specific properties of the visual receptive field. Specific response patterns were shown by cells of origin of the pyramidal tract as well as by other cells.     

Long-term potentiation of neuron-glia synapses mediated by Ca2+-permeable AMPA receptors

Interactions between neurons and glial cells in the brain may serve important functions in the development, maintenance, and plasticity of neural circuits. Fast neuron-glia synaptic transmission has been found between hippocampal neurons and NG2 cells, a distinct population of macroglia-like cells widely distributed in the brain. We report that these neuron-glia synapses undergo activity-dependent modifications analogous to long-term potentiation (LTP) at excitatory synapses, a hallmark of neuronal plasticity. However, unlike the induction of LTP at many neuron-neuron synapses, both induction and expression of LTP at neuron-NG2 synapses involve Ca2+-permeable AMPA receptors on NG2 cells.     

Rapid changes in throughput from single motor cortex neurons to muscle activity

Motor cortex output is capable of considerable reorganization, which involves modulation of excitability within the cortex. Does such reorganization also involve changes beyond the cortex, at the level of throughput from single motor cortex neurons to muscle activity? We examined such throughput during a paradigm that provided incentive for enhancing functional connectivity from motor cortex neurons to muscles. Short-latency throughput from a recorded neuron to muscle activity not present during some behavioral epochs often appeared during others. Such changes in throughput could not always be attributed to a higher neuron firing rate, to more ongoing muscle activity, or to neuronal synchronization, indicating that reorganization of motor cortex output may involve rapid changes in functional connectivity from single motor cortex neurons to alpha-motoneuron pools.     

Human motor cortex: sensory input data from single neuron recordings

Recordings were made from single neurons in the hand area of the human motor cortex while peripheral physiologic stimuli were applied. Such cells responded only to active and passive hand movements. Tactile and autditory (click) stimuli were itneffective. The majority of cells were activated only by movements of the contralateral hand, but a significant number (4 of 16) could be excited if a given movement was made by either hand. Of the cells responding to active movement, some showed an increased discharge before onset of the voluntary action. Such cells were excited by the same movement executed passively, a result that indicates sensory feedback from receptors activated by that movement.     

Descending projections to spinal motor and sensory cell groups in the monkey: cortex versus subcortex

In rhesus monkeys, corticospinal fibers have been found to terminate in motor, sensory, and internuncial cell groups. The present study reveals that the subcorticospinal fibers terminate primarily on internuncial neurons. Possible mechanisms involved in transmission of cortical and subcortical influences on motor and sensory cell groups are discussed.     

Learning induces long-term potentiation in the hippocampus

Years of intensive investigation have yielded a sophisticated understanding of long-term potentiation (LTP) induced in hippocampal area CA1 by high-frequency stimulation (HFS). These efforts have been motivated by the belief that similar synaptic modifications occur during memory formation, but it has never been shown that learning actually induces LTP in CA1. We found that one-trial inhibitory avoidance learning in rats produced the same changes in hippocampal glutamate receptors as induction of LTP with HFS and caused a spatially restricted increase in the amplitude of evoked synaptic transmission in CA1 in vivo. Because the learning-induced synaptic potentiation occluded HFS-induced LTP, we conclude that inhibitory avoidance training induces LTP in CA1.     

Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus

Norepinephrine, briefly superfused during high-frequency stimulation of the mossy fibers in the rat hippocampal slice in vitro, produced a reversible increase in the magnitude, duration, and probability of induction of long-term synaptic potentiation in the CA3 subfield. Similar results were obtained with isoproterenol, whereas propranolol or timolol reversibly blocked long-term potentiation. Norepinephrine had little apparent effect on responses obtained during low-frequency stimulation of the mossy fibers. These data suggest that norepinephrine can mediate long-lasting, frequency-dependent modulation of synaptic transmission in the mammalian brain. Furthermore, the results suggest a plausible mechanism for some of the known associative interactions between synaptic inputs to hippocampal neurons.     

Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit

Long-term potentiation (LTP), which approximates Hebb's postulate of associative learning, typically requires depolarization-dependent glutamate receptors of the NMDA (N-methyl-D-aspartate) subtype. However, in some neurons, LTP depends instead on calcium-permeable AMPA-type receptors. This is paradoxical because intracellular polyamines block such receptors during depolarization. We report that LTP at synapses on hippocampal interneurons mediating feedback inhibition is "anti-Hebbian":Itis induced by presynaptic activity but prevented by postsynaptic depolarization. Anti-Hebbian LTP may occur in interneurons that are silent during periods of intense pyramidal cell firing, such as sharp waves, and lead to their altered activation during theta activity.     

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus

A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.     

Attention units in the auditory cortex

In the course of examining single unit responses from the cortex of unrestrained and unanesthetized cats, we have come upon a population of cells that appears to be sensitive to auditory stimuli only if the cat "pays attention" to the sound source. We have described these responses, since they have not been previously reported and since they illustrate an important difference between the information which can be gleaned from experiments of this type and that obtained in the usual "acute" microelectrode experiment.     

Spatial representation in the entorhinal cortex

As the interface between hippocampus and neocortex, the entorhinal cortex is likely to play a pivotal role in memory. To determine how information is represented in this area, we measured spatial modulation of neural activity in layers of medial entorhinal cortex projecting to the hippocampus. Close to the postrhinal-entorhinal border, entorhinal neurons had stable and discrete multipeaked place fields, predicting the rat's location as accurately as place cells in the hippocampus. Precise positional modulation was not observed more ventromedially in the entorhinal cortex or upstream in the postrhinal cortex, suggesting that sensory input is transformed into durable allocentric spatial representations internally in the dorsocaudal medial entorhinal cortex.     

Dopaminergic terminals in the rat cortex

The destruction of ascending noradreniergic pathways by bilateral microinjections of 6-hydroxydopamnine made laterally to the pedunculus cerebellaris superior completely abolished the in vitro synthesis of [(3)H]norepinephrine from L-[(3)H]tyrosine in slices and in synaptosomes of the rat cortex. However, normal [(3)H]dopamine synthesis could still be observed in both cortical preparations from animals with lesions. These results provide the first biochemical support for the existence of dopaminergic terminals independent of noradrenergic terminals in the rat cortex.