Increases in Synapse Number Associated with Learning and Memory

3.1.1. Effect of Acrobatic Task Acquisition

A series of studies examining the effect of acrobatic training on synapse number comes from the work of Greenough and colleagues15-19. Adult rats were given acrobatic training during which they had to traverse elevated obstacles of an increasing difficulty for food reward over a period of 30-38 days. Three different groups of rats were used as controls. One of them received forced exercise on a treadmill, another was subjected to voluntary exercise on a freely accessible running wheel, and the third, inactive group was kept in standard laboratory cages. At the conclusion of training, the paramedian lobule of the cerebellar cortex, which is known to receive somatosensory and proprioceptive inputs from the forelimbs and hindlimbs, was examined. The estimates of synapse18,19 and Purkinje cell15,16,18,19 densities per unit volume of the molecular layer were obtained with the physical disector method. The number of synapses per Purkinje cell was calculated as the ratio of synaptic to cell numerical density. The major finding of these studies is that rats from the acrobatic group have 21-36% more synapses per Purkinje cell than those from the control groups. This learning-dependent increase in overall synapse number within the cerebellar cortex is accomplished primarily through the addition of parallel fiber synapses involving Purkinje cell spines19. A study of motor cortex layer II/III under the same experimental conditions reports similar results17. The authors additionally demonstrate that a significant learning-related increase in the number of synapses per neuron is more pronounced during the maintenance phase (days 5, 10, and 20 of training) than during the acquisition phase (days 1 and 2) of the learning curve. Taken together, these results led to the conclusion that motor learning required of the acrobatic animals, but not mere repetitive motor activity, generates new synapses in the cerebellar cortex and cerebral motor cortex. Importantly, the learning-dependent synaptic modifications observed in the cerebellar cortex of acrobatic rats persist for at least 4 weeks after completion of training18 and may, therefore, represent a substrate of long-term memory storage.

3.1.2. Effect of Skilled Reaching Task Acquisition

Skilled reaching paradigm of motor learning was used in two studies20, 21. In the earlier study20, adult rats were trained for 10 consecutive days to grasp food pellets with a front paw from a table placed 1 cm away from a slotted opening in the front of a cage until a total of 400 reaches were made per day. Rats from a motor activity control group were placed in a cage that had a small lever located beneath the opening. Pressing the lever dispensed a food pellet into a nearby receptacle. These animals were given 400 pellets per day for 10 days, used their tongue and mouth to retrieve each pellet and, hence, did not develop skilled reaching movements. After the final training session, microelectrode stimulation techniques were applied to map the motor cortex contralateral to the trained paw, following which its medial and lateral boundaries were demarcated by injections of fluorescent microspheres of different colors. The area of the motor cortex was separately measured in electrophysiologically defined regions of rostral forelimb, caudal forelimb, and hindlimb representations. Within layer V of these three regions, the numerical density of neurons and synapses was estimated with the physical disector technique, and the number of synapses per layer V pyramidal cell was calculated. It was found that rats trained on the skilled reaching task exhibited a selective areal expansion of the caudal forelimb region (i.e., the region of digit and wrist movement representations) as compared to the controls. Correspondingly, trained animals also had significantly more synapses per neuron relative to controls only within the caudal forelimb region. The subsequent study21 addressed the question of whether the observed synaptic alteration took place during the early (3 days of training) or late (7 or 10 days of training) phase of skilled reach learning. Although significant improvements in reaching accuracy occurred after 3 days, additional significant improvements were registered after 7 days, with no difference between 7- and 10-day animals. Significant expansion of distal movement representations in the caudal forelimb region was not detectable until after 10 days of training. The number of synapses per neuron was significantly higher in the caudal forelimb region of rats trained for 7 or 10 days than in the motor activity controls, indicating that the addition of synapses is characteristic of the late phase of learning when the consolidation of reaching motor skills occurs. It was hypothesized that the functional reorganization of the motor cortex is achieved through changes in cortical circuitry that involves new synapse formation. These data suggest that there may be two phases of plasticity in the motor cortex during skilled reaching training: one that is transient and does not involve an increase in synapse number; and another that is relatively long lasting and involves synaptogenesis. One untested possibility is that early-phase training increases the size and perhaps efficacy, but not the number, of synapses in the motor cortex.

3.1.3. Effect of Delay Eyeblink Conditioning

Although acrobatic task acquisition and skilled reaching training involve behavioral plasticity and therefore learning, Kleim et al.22 used the behavioral paradigm of delay eyeblink conditioning to examine whether increases in synapse number are associated with a more traditional, associative form of learning. Adult rats were given five daily training sessions, each one consisting of 100 paired presentations of a tone conditioned stimulus and periorbital shock unconditioned stimulus. During each presentation, the commencement of the conditioned stimulus preceded that of unconditioned one after which the stimuli were paired and then co-terminated. One group of control animals received explicitly unpaired presentations of the stimuli while the other was not stimulated. Synapses were quantified in the interpositus nucleus of the cerebellum, which is known to support long-term retention of the delayed eyeblink conditioned response. The numerical density of synapses and neurons was estimated in the anterior part of the interpositus nucleus with the physical disector method, and the number of synapses per neuron was calculated from synaptic and neuronal density values. Paired animals exhibited a significant increase in the percentage of trials with conditioned responses over the 5-day training period, whereas unpaired animals did not. Correspondingly, paired rats had a significantly greater number of synapses per neuron than both the unpaired and unstimulated controls. This conditioning-induced change involved asymmetrical, presumably excitatory, synapses, while the number of symmetrical, presumably inhibitory, synapses remained constant among the conditioned and control groups. It was proposed that the formation of additional excitatory synapses within the interpositus nucleus might represent a neural mechanism by which long-term memory is encoded in the cerebellum.

3.1.4. Effect of Spatial Memory Acquisition

A quantitative electron microscopic study of the hippocampal dentate gyrus used the hippocampus-dependent Morris water maze task, which involves finding a hidden escape platform, to behaviorally characterize the spatial learning capacity of adult rats23. Rats were divided into three groups that received 4, 12, or 20 training trials. A probe trial was given 3 h after the end of training, and the animals were perfusion fixed for electron microscopy immediately following the probe trial. Two control groups were used: the "swim only" group time yoked to learners without any platform to locate and the naive group with no water maze experience. The numerical densities of nonperforated axospinous synapses and granule cells were estimated per unit volume of the middle molecular layer and granule cell layer, respectively, using the physical disector technique. From these density values, the number of nonperforated synapses per granule cell was computed. Data from the probe trial showed that rats trained for 12 and 20 trials, but not four trials, displayed significant retention of platform location. In comparison to controls, a significant increase in the number of nonperforated synapses per neuron was detected in rats trained for 12 trials, but not in rats that received less (four trials) or more (20 trials) training. According to the authors, the transient nature of the observed increase in synapse number may mirror the notion that the hippocampal formation plays only an initial, time-limited role in memory acquisition and consolidation, but is not the final site of memory storage.

3.1.5. Negative Results and Their Interpretations

An experiment similar to that described above examined the hippocampal dentate gyrus and CA1 in rats given Morris water maze training on 5 consecutive days24. In this study, however, the animals were perfused for electron microscopy 6 days after the last training session (as opposed to 3 hours after the probe trial). A

control, nonspatial learning group was trained for 5 days to find a visible escape platform. The numerical density of dentate granule cells and CA1 pyramidal cells, as well as of synapses in the dentate middle molecular layer and proximal portions of CA1 basal dendrites, was assessed with the physical disector method. In both hippocampal regions studied, the numerical density of synapses and neurons was not changed. Therefore, the number of hippocampal synapses per neuron remained stable 6 days after spatial learning. Again, this negative finding could point to a transient role for hippocampal synaptic plasticity during learning.

Another quantitative electron microscopic study25 examined whether the total number of synapses in CA1 stratum radiatum is altered by trace eyeblink conditioning. The latter is a hippocampus-dependent form of associative learning that is accompanied by an enhancement of synaptic responsiveness among CA1 pyramidal neurons. Adult rabbits were trained in pairs and received either trace eyeblink conditioning or pseudoconditioning. Conditioned rabbits were given daily 80 trial sessions to a criterion of 80% conditioned responses in a session. During each trial, the conditioned (tone) and unconditioned (corneal airpuff) stimuli were presented with a stimulus-free, or trace, interval of 500 ms. Control rabbits were pseudoconditioned with an equal number of random presentations of the same stimuli. Nine pairs of conditioned and pseudoconditioned animals were examined. Brain tissue was perfusion fixed for morphological analyses 24 h after the last training session. Synapses were sampled in a systematic random manner throughout the entire extent of the CA1 stratum radiatum, and their numerical density was estimated with the physical disector technique. The entire volume of the stratum radiatum was assessed according to the unbiased principle of Cavalieri. The total synapse number, including both the perforated and nonperforated subtypes, was calculated as the product of synaptic numerical density and stratum radiatum volume. It was virtually the same in conditioned and pseudoconditioned rabbits, the difference between the group means being less than 0.1%.

As indicated above, the dynamics of learning-induced increases in synapse number is different in various brain regions, which might be related to different roles of brain regions in the acquisition and maintenance of new behaviors. For example, overall gain in the number of synapses per neuron is observed in the motor and cerebellar cortices only during the late phase of learning a complex acrobatic task, and this change in cerebellar synapses lasts at least 4 weeks after the end of training17,18. Similarly, an increase in the number of synapses per neuron occurs in the motor cortex only during the late phase, but not the early phase, of motor learning of a skilled reaching task21. In the hippocampal formation, on the other hand, synapse number per dentate granule cell is increased after an intermediate amount of training, but then returns to the control level after further training on a hippocampus-dependent version of water maze task23. These data are consistent with the concepts that motor and cerebellar cortices may be involved in a long-term retention of memories for motor skills, whereas the hippocampal formation plays only a transient role in the acquisition and consolidation of spatial memory. In the two studies demonstrating a lack of change in the number of hippocampal synapses after learning of hippocampus-dependent tasks, synapses were quantified only at a single, relatively late time point following behavioral acquisition24, 25. If quantitative ultrastructural analyses were performed in these studies at earlier time points along the acquisition/consolidation curve, the presence of additional synaptic junctions could have been detected as well.

The Donts of Treadmill Buying

The Donts of Treadmill Buying

Though competitive runners are advised to run on the road, there are several reasons why you should buy treadmills anyway. You might have a family which means that your schedule does not have the flexibility it once had.

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