Eye-blink Conditioning is Associated with Changes in Synaptic Ultrastructure in the Rabbit Interpositus Nuclei

Overview

Journal Learn Mem

Specialty Neurology

Date 2007 Jun 7

PMID 17551096

Citations 25

Authors

Andrew C W Weeks

Steve Connor

Richard Hinchcliff

Janelle C LeBoutillier

Richard F Thompson

Ted L Petit

Affiliations

Soon will be listed here.

Abstract

Eye-blink conditioning involves the pairing of a conditioned stimulus (usually a tone) to an unconditioned stimulus (air puff), and it is well established that an intact cerebellum and interpositus nucleus, in particular, are required for this form of classical conditioning. Changes in synaptic number or structure have long been proposed as a mechanism that may underlie learning and memory, but localizing these changes has been difficult. Thus, the current experiment took advantage of the large amount of research conducted on the neural circuitry that supports eye-blink conditioning by examining synaptic changes in the rabbit interpositus nucleus. Synaptic quantifications included total number of synapses per neuron, numbers of excitatory versus inhibitory synapses, synaptic curvature, synaptic perforations, and the maximum length of the synapses. No overall changes in synaptic number, shape, or perforations were observed. There was, however, a significant increase in the length of excitatory synapses in the conditioned animals. This increase in synaptic length was particularly evident in the concave-shaped synapses. These results, together with previous findings, begin to describe a sequence of synaptic change in the interpositus nuclei following eye-blink conditioning that would appear to begin with structural change and end with an increase in synaptic number.

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References

Mackenzie P, Kenner G, Prange O, Shayan H, Umemiya M, Murphy T . Ultrastructural correlates of quantal synaptic function at single CNS synapses. J Neurosci. 1999; 19(12):RC13. PMC: 6782679. View

Geinisman Y, deToledo-Morrell L, MORRELL F, Heller R, Rossi M, Parshall R . Structural synaptic correlate of long-term potentiation: formation of axospinous synapses with multiple, completely partitioned transmission zones. Hippocampus. 1993; 3(4):435-45. DOI: 10.1002/hipo.450030405. View

Weeks A, Ivanco T, Leboutillier J, Racine R, Petit T . Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus: I. The intermediate maintenance phase. Synapse. 1999; 31(2):97-107. DOI: 10.1002/(SICI)1098-2396(199902)31:2<97::AID-SYN2>3.0.CO;2-D. View

Gomi H, Sun W, Finch C, Itohara S, Yoshimi K, Thompson R . Learning induces a CDC2-related protein kinase, KKIAMRE. J Neurosci. 1999; 19(21):9530-7. PMC: 6782914. View

Kim J, Thompson R . Cerebellar circuits and synaptic mechanisms involved in classical eyeblink conditioning. Trends Neurosci. 1997; 20(4):177-81. DOI: 10.1016/s0166-2236(96)10081-3. View

Black J, Isaacs K, Anderson B, Alcantara A, Greenough W . Learning causes synaptogenesis, whereas motor activity causes angiogenesis, in cerebellar cortex of adult rats. Proc Natl Acad Sci U S A. 1990; 87(14):5568-72. PMC: 54366. DOI: 10.1073/pnas.87.14.5568. View

Fifkova E . Actin in the nervous system. Brain Res. 1985; 356(2):187-215. View

Greenough W, Larson J, Withers G . Effects of unilateral and bilateral training in a reaching task on dendritic branching of neurons in the rat motor-sensory forelimb cortex. Behav Neural Biol. 1985; 44(2):301-14. DOI: 10.1016/s0163-1047(85)90310-3. View

Bracha V, Irwin K, Webster M, Wunderlich D, Stachowiak M, Bloedel J . Microinjections of anisomycin into the intermediate cerebellum during learning affect the acquisition of classically conditioned responses in the rabbit. Brain Res. 1998; 788(1-2):169-78. DOI: 10.1016/s0006-8993(97)01535-7. View

10.

Hansel C, Linden D, DAngelo E . Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci. 2001; 4(5):467-75. DOI: 10.1038/87419. View

11.

Chen G, Steinmetz J . Intra-cerebellar infusion of NMDA receptor antagonist AP5 disrupts classical eyeblink conditioning in rabbits. Brain Res. 2001; 887(1):144-56. DOI: 10.1016/s0006-8993(00)03005-5. View

12.

Geinisman Y, Disterhoft J, Gundersen H, McEchron M, Persina I, Power J . Remodeling of hippocampal synapses after hippocampus-dependent associative learning. J Comp Neurol. 2000; 417(1):49-59. View

13.

Steinmetz J, Lavond D, Thompson R . Classical conditioning in rabbits using pontine nucleus stimulation as a conditioned stimulus and inferior olive stimulation as an unconditioned stimulus. Synapse. 1989; 3(3):225-33. DOI: 10.1002/syn.890030308. View

14.

Steinmetz J, Sengelaub D . Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus. Behav Neural Biol. 1992; 57(2):103-15. DOI: 10.1016/0163-1047(92)90593-s. View

15.

Thompson R, Thompson J, Kim J, Krupa D, SHINKMAN P . The nature of reinforcement in cerebellar learning. Neurobiol Learn Mem. 1998; 70(1-2):150-76. DOI: 10.1006/nlme.1998.3845. View

16.

Geinisman Y, deToledo-Morrell L, MORRELL F . Induction of long-term potentiation is associated with an increase in the number of axospinous synapses with segmented postsynaptic densities. Brain Res. 1991; 566(1-2):77-88. DOI: 10.1016/0006-8993(91)91683-r. View

17.

Weeks A, Ivanco T, Leboutillier J, Racine R, Petit T . Sequential changes in the synaptic structural profile following long-term potentiation in the rat dentate gyrus: III. Long-term maintenance phase. Synapse. 2001; 40(1):74-84. DOI: 10.1002/1098-2396(200104)40:1<74::AID-SYN1028>3.0.CO;2-D. View

18.

Hesslow G, Svensson P, Ivarsson M . Learned movements elicited by direct stimulation of cerebellar mossy fiber afferents. Neuron. 2000; 24(1):179-85. DOI: 10.1016/s0896-6273(00)80831-4. View

19.

Turner A, Greenough W . Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron. Brain Res. 1985; 329(1-2):195-203. DOI: 10.1016/0006-8993(85)90525-6. View

20.

Buchs P, Muller D . Induction of long-term potentiation is associated with major ultrastructural changes of activated synapses. Proc Natl Acad Sci U S A. 1996; 93(15):8040-5. PMC: 38871. DOI: 10.1073/pnas.93.15.8040. View