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Biomedical subjects

R F Thompson

Publications and source records attributed to R F Thompson.

242 records · Page 14Linked to original sources
PubMedDate not supplied

Classical conditioning: the Rosetta stone for brain substrates of age-related deficits in learning and memory.

The three chapters on the use of classical conditioning paradigms to investigate neurobiological and behavioral substrates of memory impairments with aging are in close agreement on all key issues. Based on these chapters, it is argued here that classical conditioning of discrete behavioral responses in rabbit and other mammals is among the most promising animal models of the human condition in which to analyze brain mechanisms of normally occurring age-related deficits in learning and memory.

Aging↗
PubMedDate not supplied

Temporal specificity of long-term depression in parallel fiber--Purkinje synapses in rat cerebellar slice.

The phenomenon of cerebellar long-term depression (LTD), a decrease of synaptic strength between the parallel fibers (PFs) and Purkinje cells after conjunctive activation of PFs and the climbing fibers (CFs), is implicated as a cellular mechanism for motor learning. We have characterized a field-potential recording technique in cerebellar slice and have used the technique to examine the temporal conditions for cerebellar LTD induction in an attempt to examine the relevance of LTD to associative conditioning. Interstimulus intervals (ISIs) between onsets of PF and CF activation and the number of paired stimuli (pairings) were examined. LTD has distinct temporal specificity that seems to be constrained by inhibitory interneurons and can be masked by excessive stimulation. When 100 paired stimuli were given to PFs and CFs, LTD was induced with an ISI of 250 msec (PF activation preceding CF activation). In contrast, a smaller forward (125 msec), simultaneous (0 msec), or backward (-250 msec) ISIs were not effective for inducing LTD. However, the blockade of GABAA receptor-mediated inhibition made it possible to induce LTD with 100 pairs of simultaneous stimulations. Furthermore, by increasing the number of pairings to 600, significant LTD was observed with all four interstimulus intervals. These results suggest that temporal conditions for LTD induction share some similarity to associative learning of discrete motor responses.

Animals↗
PubMedDate not supplied

Reversible inactivation of the cerebellar interpositus nucleus completely prevents acquisition of the classically conditioned eye-blink response.

Numerous studies from several laboratories report that temporary inactivation of the cerebellar interpositus nucleus and regions of overlying cortex during eye-blink conditioning completely prevents acquisition of the conditioned eye-blink response (CR) without affecting the ability to learn the CR in subsequent training without inactivation. Recently, these results have been challenged by the suggestion that learning was not completely blocked in these studies. Instead, it has been suggested that low levels of responses on test sessions might represent a retarded form of learning caused by drug effects on cerebellar cortex. The present study was designed to address this issue directly. Very low doses of muscimol were used to selectively inactivate the interpositus nucleus of rabbits during five conditioning sessions. Animals performed no significant levels of CRs during those sessions. Training was continued four more sessions without any inactivations to test whether any learning had occurred during the previous five sessions. Detailed analysis of responses during session six revealed that learning was completely blocked by the low doses of muscimol infused into the interpositus during the first five sessions. Animals subsequently acquired the CR normally. These results confirm and extend the original findings that appropriate lesions (either temporary or permanent) of the interpositus nucleus completely prevent acquisition of the conditioned eye-blink response. Other issues regarding reversible inactivation studies are also discussed.

Animals↗
PubMedDate not supplied

Effects of paired and unpaired eye-blink conditioning on Purkinje cell morphology.

This experiment addressed (1) the importance of conjunctive stimulus presentation for morphological plasticity of cerebellar Purkinje cells and inhibitory interneurons and (2) whether plasticity is restricted to the spiny branches of Purkinje cells, which receive parallel fiber input. These issues were investigated in naive rabbits and in rabbits that received paired or unpaired presentations of the conditioned stimulus (CS) and unconditioned stimulus (US). To direct CS input to the cerebellar cortex, pontine stimulation served as the CS. Air puffs to the cornea served as the US. Paired condition rabbits received pontine stimulation for 350 msec paired with a coterminating 100-msec air puff. Unpaired condition rabbits received the same stimuli in a pseudorandom order at 1- to 32-sec intervals. Rabbits were trained for a mean of 12 days. Naive rabbits received no treatment. In Golgi-stained Purkinje neurons in lobule HVI, total dendritic length, main branch length, total spiny branch length, and number of spiny branch arbors were all greater in the naive group than in the paired and unpaired groups, which did not differ. No differences were found between the hemispheres ipsilateral and contralateral to the trained eye. The dendritic length and number of branches for inhibitory interneurons did not differ across groups. The Purkinje cell morphological changes detected with these methods do not appear to be uniquely related to the conjunctive activation of the CS and US in the paired condition.

Animals↗
PubMedDate not supplied

Impaired eye-blink conditioning in waggler, a mutant mouse with cerebellar BDNF deficiency.

In addition to their trophic functions, neurotrophins are also implicated in synaptic modulation and learning and memory. Although gene knockout techniques have been used widely in studying the roles of neurotrophins at molecular and cellular levels, behavioral studies using neurotrophin knockouts are limited by the early-onset lethality and various sensory deficits associated with the gene knockout mice. In the present study, we found that in a spontaneous mutant mouse, waggler, the expression of brain-derived neurotrophic factor (BDNF) was selectively absent in the cerebellar granule cells. The cytoarchitecture of the waggler cerebellum appeared to be normal at the light microscope level. The mutant mice exhibited no sensory deficits to auditory stimuli or heat-induced pain. However, they were massively impaired in classic eye-blink conditioning. These results suggest that BDNF may have a role in normal cerebellar neuronal function, which, in turn, is essential for classic eye-blink conditioning.

Animals↗
PubMedDate not supplied

Transgenic brain-derived neurotrophic factor modulates a developing cerebellar inhibitory synapse.

Brain-derived neurotrophic factor (BDNF) has been shown to promote synapse formation and maturation in neurons of many brain regions, including inhibitory synapses. In the cerebellum, the Golgi cell-granule cell GABAergic synaptic responses undergo developmental transition from slow-decaying to fast-decaying kinetics, which parallels a developmental increase of GABA(A) receptor alpha6 subunit expression in the cerebellar granule cells. In culture, BDNF accelerates the expression of GABA(A) receptor alpha6 subunit expression in granule cells. Here we examined synaptic GABA(A) response kinetics in BDNF transgenic mice. The mutant mouse, which carries a BDNF transgene driven by a beta-actin promoter, overexpresses BDNF (two- to fivefold increase compared with wild types) in all brain regions. Recordings of the spontaneous GABA(A) responses indicate that the decay time constant of the GABAergic responses decreases during early postnatal development; this transition is accelerated in the BDNF transgenic mouse. The amplitude of the spontaneous GABA(A) responses was also larger in the transgenic mouse than in the wild-type mouse. However, the frequency of the spontaneous GABA(A) responses were not different between the two groups. Our results suggest that BDNF may modulate GABAergic synapse maturation in the cerebellum.

Aging↗
PubMedDate not supplied

Percutaneous transnasal sphenoidotomy with sphenoid window.

Ten percutaneous transnasal sphenoidotomies were performed in nine children; and in seven, a sphenoid window was also created. All procedures were performed in the special procedures laboratory, with biplane fluoroscopic guidance used in each case. Under general anesthesia, with the child in the supine position, a 14-gauge antral trocar was placed transnasally into the sphenoid sinus. The sinus was aspirated and material was obtained for culture. A Takahashi forceps was placed via the same tract into the sphenoid sinus. The cusps were centered across the anterior cortex, and under fluoroscopic visualization, opened and rotated 360 degrees, creating a sphenoid window. All procedures were completed without complication, and no child required further surgery.

Adolescent↗