Learning and memory. FESN Study Group.
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Animals↗
Biomedical subjects
M F Bear
Publications and source records attributed to M F Bear.
Brain-derived neurotrophic factor alters the synaptic modification threshold in visual cortex.
The effects of brain-derived neurotrophic factor (BDNF) were investigated on synaptic transmission and two forms of activity-dependent synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD), in visual cortex slices prepared from young (P21 -28) rats. The slices treated for 2-5 h in BDNF showed no difference from control slices when a 'strong' tetanus was used (theta-burst stimulation) to elicit a maximal level of LTP but displayed significantly greater synaptic potentiation in response to a 'weak' (20 Hz) tetanus. The BDNF-treated slices also showed significantly less LTD in response to a 1 Hz tetanus. Thus, BDNF treatment alters the relationship between stimulation frequency and synaptic plasticity in the visual cortex, shifting the modification threshold to the left. The effects of BDNF on LTP and LTD induction may be attributed to the significant enhancement of synaptic responses that was observed during conditioning stimulation. These data suggest that one role of BDNF during development of the visual cortex may be to modulate the properties of synaptic plasticity, enhancing synaptic strengthening and reducing synaptic weakening processes which contribute to the formation of specific synaptic connections.
Animals↗
Two methods of catecholamine depletion in kitten visual cortex yield different effects on plasticity.
As first clearly demonstrated by the experiments of Wiesel and Hubel, the developing visual cortex is exquisitely sensitive to sensory deprivation. Temporary closure of one eye of a kitten during a critical period that extends from 3 weeks to 3 months of age results in a dramatic cortical reorganization such that most neurones, originally binocularly driven, are dominated exclusively by the open eye. Recently, attention has been directed to chemical factors which may influence the degree of plasticity during the critical period. The work of Kasamatsu and pettigrew suggests that cortical catecholamines, especially noradrenaline (NA), are essential for the normal plastic response to visual deprivation. In an effort to clarify the role of NA in visual cortical plasticity, we have monocularly deprived kittens whose cortex had been depleted of catecholamines by the neurotoxin 6-hydroxydopamine (6-OHDA). We used two strategies to deplete cortical NA: the first, pioneered by Kasamatsu el al., utilized osmotic minipumps to deliver 6-OHDA to visual cortex; the second involved systemic neonatal injections of 6-OHDA, a technique which has proved effective in rodents. We found, using high-pressure liquid chromatography (HPLC), that both techniques produced a substantial reduction in the level of cortical NA. However, single unit recording in area 17 revealed that the plastic response to monocular deprivation (MD) was only diminished in the kittens depleted by minipump.
Animals↗
Modulation of visual cortical plasticity by acetylcholine and noradrenaline.
During a critical period of postnatal development, the temporary closure of one eye in kittens will permanently shift the ocular dominance (OD) of neurones in the striate cortex to the eye that remains open. The OD plasticity can be substantially reduced if the cortex is infused continuously with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) during the period of monocular deprivation, an effect that has been attributed to selective depletion of cortical noradrenaline. However, several other methods causing noradrenaline (NA) depletion leave the plasticity intact. Here we present a possible explanation for the conflicting results. Combined destruction of the cortical noradrenergic and cholinergic innervations reduces the physiological response to monocular deprivation although lesions of either system alone are ineffective. We also find that 6-OHDA can interfere directly with the action of acetylcholine (ACh) on cortical neurones. Taken together, our results suggest that intracortical 6-OHDA disrupts plasticity by interfering with both cholinergic and noradrenergic transmission and raise the possibility that ACh and NA facilitate synaptic modifications in the striate cortex by a common molecular mechanism.
Acetylcholine↗
A current source density analysis of evoked responses in slices of adult rat visual cortex: implications for the regulation of long-term potentiation.
In slices of visual cortex, long-term potentiation (LTP) of synaptic responses in layer III can be evoked by high-frequency stimulation of a site in the middle of the cortical thickness, corresponding mainly to layer IV. In contrast, stimulation of the white matter-layer VI border typically fails to evoke LTP in adult visual cortex unless GABAA receptors are partially blocked. We performed current-source density (CSD) analysis to determine how the patterns of cortical activation compare under these different stimulation conditions. Single-pulse stimulation of the middle layers (corresponding to layer IV and superficial V) and the deep layers (corresponding to white matter and deep layer VI) yielded very similar CSD patterns. The major current sinks were located within 500 mu m of the pia, corresponding to layers II and III, regardless of the stimulation site. The amplitude of all current sinks was diminished, and the latency was increased, in the presence of high concentrations of divalent cations (12 mM Ca2+ and 12 mM mg2+). Nonetheless, the major synaptic current sink was still present at a depth of approximately 400 microns regardless of the site of stimulation, indicating that stimulation of either site leads to monosynaptic EPSCs in layer III. However, superficial sinks, at a depth of approximately 200 microns, were virtually eliminated by high concentrations of divalent cations after deep layer stimulation, but not after middle layer stimulation, suggesting that stimulation at the two sites recruits different monosynaptic circuits. This conclusion was supported by experiments using paired-pulse stimulation of the two sites (12.5 ms interstimulus interval). While there was little evidence of a paired-pulse interaction after stimulation of the middle layers, there was marked paired-pulse suppression of superficial layer III current sinks after stimulation of the deep layers. Taken together, the data suggest a model in which deep layer stimulation activates the dendrites of layer III cells by a monosynaptic route and by a disynaptic route. The disynaptic input originates in the middle cortical layers and is controlled by inhibition. Differences in synaptic plasticity evoked from the different sites could be explained if the recruitment of middle layer inputs were required for the generation of LTP in layer III.
Animals↗
Temporally graded retrograde amnesia following separate and combined lesions of the perirhinal cortex and fornix in the rat.
The involvement of the perirhinal cortex and the fornix in retrograde and anterograde amnesia in the rat was investigated in this experiment. Male Sprague-Dawley rats were trained on a series of five visual discrimination problems at distinct time intervals prior to receiving bilateral, electrolytic lesions of the perirhinal cortex or the fornix, combined lesions of both these structures, or sham operations. Following recovery from surgery, rats were retested on the preoperatively learned discrimination problems, as well as learning a new discrimination and discrimination reversal. Results indicated that all animals with lesions exhibited temporally graded retrograde amnesia, whereby memories acquired in the recent past (1-3 weeks) were impaired, and memories acquired in the remote past (6-8 weeks) were spared. There was no difference in the magnitude of retrograde amnesia between the three lesion groups. Animals in the perirhinal, fornix, and combined lesion groups were able to learn a new discrimination problem at a rate comparable to control rats; however, the animals with lesions were impaired at learning the discrimination reversal. The perirhinal, fornix, and combined lesion animals also exhibited a significantly faster forgetting rate over a 2-week retention interval than control rats. These results suggest that medial temporal structures including the perirhinal cortex and the fornix are involved in the consolidation of mnemonic information and that their involvement in this process occurs over a discrete period of time.
Amnesia↗