LTP and LTD vary with layer in rodent visual cortex

Vision Research 44 (2004) 3377–3380 www.elsevier.com/locate/visres

LTP and LTD vary with layer in rodent visual cortex Nigel Daw *, Yan Rao, Xue-Feng Wang, Quentin Fischer, Yupeng Yang Department of Ophthalmology, Yale University Medical School, 330 Cedar Street, New Haven, CT 06520-8061, USA Received 25 May 2004; received in revised form 29 August 2004

Abstract Mechanisms of plasticity in the visual cortex have been studied with long-term potentiation (LTP), long-term depression (LTD) and ocular dominance plasticity (ODP). It is now possible to compare results from these three forms of plasticity using knockout mice, and also by pharmacological manipulations. A review of the literature shows that if both LTP and LTD are completely abolished, then ODP will also be abolished. In other situations, there is little correlation. We hypothesize that this lack of correlation occurs because the mechanisms for LTP and LTD vary with layer in the visual cortex, and results show that they do. Ó 2004 Elsevier Ltd. All rights reserved. Keywords: Ocular dominance plasticity; Long-term potentiation; Long-term depression; Visual cortex

1. Background With the advent of knockout mutations in mice, a number of experiments have now been done to compare the mechanisms of long-term potentiation (LTP) and long-term depression (LTD) with those of ocular dominance plasticity (ODP) in the visual cortex. These experiments supplement those done previously using antagonists to various putative factors (see Table 1). One general rule is that if both LTP and LTD are abolished, then ODP is also abolished. There are now two well established examples of this rule, using protein kinase A (PKA) antagonists, and N-methyl-D -aspartate (NMDA) antagonists. The NMDA antagonist D -amino-phosphonovalerate (APV) has been known for some time to be involved in plasticity in the hippocampus, and also abolishes ODP in the visual cortex (Bear, Kleinschmidt, Gu, & Singer, 1990). This is a specific effect on plasticity, and is not due simply to a reduction in the activity reaching *

Corresponding author. Tel.: +1 203 737 4096; fax: +1 203 785 7401. E-mail address: [email protected] (N. Daw). 0042-6989/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.visres.2004.09.004

the cortex (Daw et al., 1999a). APV also abolishes LTP (Artola & Singer, 1987) and LTD (Dudek & Bear, 1992). Another molecule known to be involved in plasticity in the hippocampus and Drosophila is PKA. Antagonists to PKA also abolish ocular dominance plasticity (Beaver, Ji, Fischer, & Daw, 2001), LTP and LTD (Liu, Rao, & Daw, 2003). There are several cases where LTD is linked to ODP, but LTP is not. These include knockout of the RIIb subunit of PKA, where ODP is absent and LTD is absent, but LTP is present (Fischer et al., 2004), knockout of the A kinase anchoring protein AKAP 79/150, with a similar result (Fischer, Yang, Jakobsdottir, McKnight, & Daw, 2003; Rao, McKnight, & Daw, 2003) and knockout of the GABA synthesizing enzyme GAD65 where ODP (Hensch et al., 1998a) and LTD (Choi, Morales, Lee, & Kirkwood, 2002) are again both absent. In the case of application of protein kinase G (PKG) antagonists, the reverse occurs––ODP and LTD are present, while LTP is absent (Beaver et al., 2001; Liu et al., 2003). It is tempting to postulate from these results that ODP is related to LTD but not to LTP. This would tally with the results of Heynen et al. (2003), who have shown that monocular deprivation sets into motion the same

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layers of the visual cortex. The LTP and LTD results nearly all come from stimulation of layer IV with recordings of field potentials in layers II and III (Table 1). We therefore hypothesized that the lack of correlation may occur because there are different mechanisms of plasticity in different layers. In order to test this hypothesis, we decided to record single cells with whole cell recordings in various layers, and stimulate for the predominant flow of information in the cortex, stimulating white matter for recordings in layer IV, layer IV for recordings in layers II and III, and layers II and III for recordings in layers V and VI (Lund & Boothe, 1975). As a first step, we compared results with the NMDA antagonist APV with those from various metabotropic glutamate receptor antagonists, bathing the whole slice with the antagonists, since we have accumulated considerable information on the laminar distribution of these receptors (Beaver, Ji, & Daw, 1999; Jin, Beaver, Ji, & Daw, 2001; Reid & Daw, 1997; Wang, Jin, & Daw, 1998). The results for LTP elicited by theta burst stimulation are shown in Table 2 (Wang & Daw, 2003). Essentially LTP in layers II and III depends on NMDA receptors, and partially on the mGluR1 receptor. LTP in layer V depends on NMDA receptors and mGluR5, and partially on mGluR1. LTP in layer VI depends on mGluR1 but not on NMDA receptors, and the mGluR5 antagonist produces an enhanced potentiation. The result seen in layer VI is like that seen in mossy fiber LTP in the hippocampus (Conquet et al., 1994). The result seen in layer V is like that seen in CA1 and dentate gyrus in hippocampus (Lu et al., 1997; Manahan-Vaughan et al., 2003). The result seen in layers II and III is unique to visual cortex. The results for LTD elicited by low frequency stimulation of 1 Hz for 10 min are shown in Table 3 (Rao & Daw, 2004). Essentially LTD in layers II/III and V depends on NMDA receptors, but not on mGluR receptors. LTD in layer VI, on the other hand, depends on mGluR receptors, probably group I mGluRs, but not on NMDA receptors. Thus for both LTP and LTD NMDA receptors play some role in layers II/III and V, but none in layer VI, whereas metabotropic glutamate receptors play a role in layer VI, but little in

Table 1 Correlation of ocular dominance plasticity, LTP and LTD Treatment

ODP

LTP

LTD

PKA antagonist NMDA antagonist GAD65 knockout PKA RIIb knockout MAP kinase inhibitors PKA RIIa knockout AKAP150 knockout PKA RIb knockout PKG antagonist mGluR2 knockout BDNF application/ overexpression

Absent Absent Absent Absent Absent Reduced Reduced Present Present Present Early

Absent Absent Present Present Absent Reduced Present Some forms absent Absent Not tested Increased

Absent Absent Absent Absent Not tested Present Absent Absent Present Absent Reduced

molecular mechanisms as LTD, and that monocular deprivation occludes the subsequent induction of LTD. It is also consistent with the results of Antonini and Stryker (1996), who have shown that retraction of geniculocortical terminals from the deprived eye occurs before expansion of the geniculocortical terminals from the non-deprived eye, if one assumes that retraction of terminals is associated with LTD and expansion of terminals is associated with LTP. Unfortunately there are several counter examples where ODP is not related to LTD (see Table 1). Activation of the metabotropic glutamate receptor mGluR2 produces LTD, and mice mutant for mGluR2 do not have LTD, but do have ODP (Renger et al., 2002). Mice mutant for the RIb subunit of PKA also lack LTD but have ODP (Hensch et al., 1998b). Moreover, in mice mutant for the RIIa subunit of PKA, LTD is not significantly reduced, but ODP is (Rao et al., 2004). Furthermore, application of BDNF produces LTP and blocks LTD (Akaneya, Tsumoto, & Hatanaka, 1996, 1997), whereas overexpression of BDNF induces ODP early (Hanover, Huang, Tonegawa, & Stryker, 1999). The relationship is therefore complex. 2. Hypothesis and results The ODP results that have been cited so far are all results from recording a number of single cells from all Table 2 Variation of LTP with layer Treatment

II/III

V

VI

Control

Potentiation 234 ± 13%

Potentiation 175 ± 9%

Potentiation 189 ± 9%

NMDA antagonist

No change 93 ± 4%

Depression 84 ± 2%

Potentiation 169 ± 4%

mGluR1 antagonist

Reduced potentiation 134 ± 4%

Reduced potentiation 134 ± 3%

No change 111 ± 3%

mGluR5 antagonist

Reduced potentiation 170 ± 2%

No change 103 ± 2%

Enhanced potentiation 309 ± 8%

N. Daw et al. / Vision Research 44 (2004) 3377–3380 Table 3 Variation of LTD with layer Treatment

II/III

V

VI

Control

Depression 70 ± 5%

Depression 63 ± 7%

Depression 65 ± 7%

NMDA antagonist

No change 93 ± 6%

No change 103 ± 9%

Depression 77 ± 5%

mGluR antagonist

Depression 70 ± 3%

Depression 71 ± 7%

No change 94 ± 10%

GDP-b-S

Reduced depression 80 ± 5%

Group II mGluR antagonist

Depression 55 ± 8%

Group I mGluR antagonist

No change 93 ± 5%

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was the species for LTP, LTD and ODP, so those comparisons are independent of species. In spite of all the caveats, the basic principle has been established. The mechanisms of LTP and LTD vary with the layer of the recording electrode, and this should be considered in future experiments on plasticity in the visual cortex. We know that there are different critical periods for different layers for the effects of monocular deprivation in visual cortex (Daw, Fox, Sato, & Czepita, 1992) and that changes occur in layers II/III before they occur in layer IV (Trachtenberg, Trepel, & Stryker, 2000). This may very well occur because there are different mechanisms of plasticity in different layers.

Acknowledgments layers II/III and V. Neither LTP nor LTD was seen when recording in layer IV with stimulation at the layer VI/white matter boundary, so this is not included in the tables.

This work was supported by PHS Grant No. RO1 EY11353 and Connecticut Lions Eye Research Foundation. Nigel Daw is a Senior Scientific Investigator of Research to Prevent Blindness.

3. Discussion References It is clear that considerably more work will be required to follow-up on these results. The site of stimulation can be varied to include other layers and lateral placements. Ideally one would like to see stimulation of a single cell, as well as recordings from a single cell. The age of the animal can be varied––most recordings in the present series of experiments were carried out in animals 3–4 weeks of age. The function of both NMDA receptors and metabotropic glutamate receptors is known to vary with age (Daw, Reid, & Beaver, 1999b; Fox, Sato, & Daw, 1989) and LTP and LTD also vary with age (Dudek & Friedlander, 1996; Kirkwood, Lee, & Bear, 1995; Yoshimura, Ohmura, & Komatsu, 2003). Other ways of producing LTP and LTD could be included besides the theta burst and low frequency stimulation used in the current series of experiments. Finally, other factors should be studied besides the glutamatergic receptors that have been shown to have a role in ODP, LTP and LTD. Unfortunately this represents an exponentially expanding set of experiments if all variables are included. We should also point out that we have combined results from a variety of species in this review. Most LTP and LTD experiments come from slices of rat or mouse visual cortex. Most ODP experiments come from recordings in cat or mouse visual cortex. However, there is little evidence that the effects of monocular deprivation vary between these species, except for the anatomical results in layer IV, where rodents do not have segregated left and right eye columns, whereas cats do. In cases where knockout mutants were used, mouse

Akaneya, Y., Tsumoto, T., & Hatanaka, Y. (1996). Brain-derived neurotrophic factor blocks long-term depression in rat visual cortex. Journal of Neurophysiology, 76, 4198–4201. Akaneya, Y., Tsumoto, T., Kinoshita, S., & Hatanaka, Y. (1997). Brain-derived neurotrophic factor enhances long-term potentiation in rat visual cortex. Journal of Neuroscience, 17, 6707–6716. Antonini, A., & Stryker, M. P. (1996). Plasticity of geniculocortical afferents following brief or prolonged monocular occlusion in the cat. Journal of Comparative Neurology, 369, 64–82. Artola, A., & Singer, W. (1987). Long-term potentiation and NMDA receptors in rat visual cortex. Nature, 330, 649–652. Bear, M. F., Kleinschmidt, A., Gu, Q., & Singer, W. (1990). Disruption of experience dependent synaptic modifications in striate cortex by infusion of an NMDA receptor antagonist. Journal of Neuroscience, 10, 909–925. Beaver, C. J., Ji, Q.-H., & Daw, N. W. (1999). Effect of the Group II metabotropic glutamate agonist, 2R, 4R-APDC, varies with age, layer and visual experience in the visual cortex. Journal of Neurophysiology, 82, 86–93. Beaver, C. J., Ji, Q.-H., Fischer, Q. S., & Daw, N. W. (2001). cAMPdependent protein kinase mediates ocular dominance shifts in cat visual cortex. Nature Neuroscience, 4, 159–163. Choi, S. Y., Morales, B., Lee, H. K., & Kirkwood, A. (2002). Absence of long-term depression in the visual cortex of glutamic acid decarboxylase-65 knock-out mice. Journal of Neuroscience, 22, 5271–5276. Conquet, F., Bashir, Z. I., Davies, C. H., Daniel, H., Ferraguti, F., Bordi, F., et al. (1994). Motor deficit and impairment of synaptic plasticity in mice lacking mGluR1. Nature, 372, 237–244. Daw, N. W., Fox, K. D., Sato, H., & Czepita, D. (1992). Critical period for monocular deprivation in the cat visual cortex. Journal of Neurophysiology, 67, 197–202. Daw, N. W., Gordon, B., Fox, K. D., Flavin, H. J., Kirsch, J. D., Beaver, C. J., et al. (1999a). Injection of MK-801 affects ocular dominance shifts more than visual activity. Journal of Neurophysiology, 81, 204–215.

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N. Daw et al. / Vision Research 44 (2004) 3377–3380

Daw, N. W., Reid, S. M., & Beaver, C. J. (1999b). Development and function of metabotropic glutamate receptors in cat visual cortex. Journal of Neurobiology, 41, 102–107. Dudek, S. M., & Bear, M. F. (1992). Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D aspartate receptor blockade. Proceedings of the National Academy of Sciences USA, 89, 4363–4367. Dudek, S. M., & Friedlander, M. J. (1996). Developmental downregulation of LTD in cortical layer IV and its independence of modulation by inhibition. Neuron, 16, 1097–1106. Fischer, Q. S., Yang, Y. P., Jakobsdottir, K. B., McKnight, G. S., & Daw, N. W. (2003). Type II PKA and its localization by AKAP150 is crucial for ocular dominance plasticity in mice. Society for Neuroscience Abstracts, 29, 37.9. Fischer, Q. S., Beaver, C. J., Yang, Y. P., Rao, Y., Jakobsdottir, K. B., & Storm, D. R. (2004). Requirement for the RIIb isoform of PKA, but not calcium-stimulated adenylyl cyclase, in visual cortical plasticity. Journal of Neuroscience, 24(42). Fox, K. D., Sato, H., & Daw, N. W. (1989). The location and function of NMDA receptors in cat and kitten visual cortex. Journal of Neuroscience, 9, 2443–2454. Hanover, J. L., Huang, Z. J., Tonegawa, S., & Stryker, M. P. (1999). Brain-derived neurotrophic factor overexpression induces precocious critical period in mouse visual cortex. Journal of Neuroscience, 19, RC40. Hensch, T. K., Fagiolini, M., Mataga, N., Stryker, M. P., Baekkeskov, S., & Kash, S. F. (1998a). Local GABA circuit control of experience-dependent plasticity in developing visual cortex. Science, 282, 1504–1508. Hensch, T. K., Gordon, J. A., Brandon, E. P., McKnight, G. S., Iderzda, R. L., & Stryker, M. P. (1998b). Comparison of plasticity in vivo and in vitro in the developing visual cortex of normal and protein kinase A R1b-deficient mice. Journal of Neuroscience, 18, 2108–2117. Heynen, A. J., Yoon, B.-J., Liu, C.-H., Chung, H. J., Huganir, R. L., & Bear, M. F. (2003). Molecular mechanism for loss of visual cortical responsiveness following brief monocular deprivation. Nature Neuroscience, 6, 854–862. Jin, X.-T., Beaver, C. J., Ji, Q.-H., & Daw, N. W. (2001). Effect of the group I metabotropic glutamate agonist DHPG on the visual cortex. Journal of Neurophysiology, 86, 1622–1631. Kirkwood, A., Lee, H. K., & Bear, M. F. (1995). Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience. Nature, 375, 328–331. Liu, S., Rao, Y., & Daw, N. W. (2003). Roles of protein kinase A and protein kinase G in synaptic plasticity in the visual cortex. Cerebral Cortex, 13, 864–869.

Lu, Y. M., Jia, Z., Janus, C., Henderson, J. T., Gerlai, R., Wojtowicz, J. M., et al. (1997). Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. Journal of Neuroscience, 17, 5196–5205. Lund, J. S., & Boothe, R. G. (1975). Interlaminar connections and pyramidal neuron organisation in the visual cortex, area 17, of the macaque monkey. Journal of Comparative Neurology, 159, 305–334. Manahan-Vaughan, D., Ngomba, R. T., Storto, M., Kulla, A., Catania, M. V., Chiechio, S., et al. (2003). An increased expression of the mGluR5 receptor protein following LTP induction at the perforant path-dentate gyrus synapse in freely moving rats. Neuropharmacology, 44, 17–25. Rao, Y., McKnight, G. S., & Daw, N. W. (2003). Synaptic plasticity in PKA RIIalpha and AKAP150 knockout mouse visual cortex. Society for Neuroscience Abstracts, 29, 584.11. Rao, Y., Fischer, Q. S., Yang, Y., McKnight, G. S., LaRue, A., & Daw, N. W. (2004). Reduced ocular dominance plasticity and long-term potentiation in developing visual cortex of protein kinase A RIIa mutant mice. European Journal of Neuroscience, 20, 837–842. Rao, Y., & Daw, N. W. (2004). Layer variations of long-term depression in rat visual cortex. Journal of Neurophysiology, doi: 10.1152/jn.00298.2004. Reid, S. M., & Daw, N. W. (1997). Activation of metabotropic glutamate receptors has different effects in different layers of cat visual cortex. Visual Neuroscience, 14, 83–88. Renger, J. J., Hartman, K. N., Tsuchimoto, Y., Yokoi, M., Nakanishi, S., & Hensch, T. K. (2002). Experience-dependent plasticity without long-term depression by type 2 metabotropic glutamate receptors in developing visual cortex. Proceedings of the National Academy of Sciences USA, 99, 1041–1046. Trachtenberg, J. L., Trepel, C., & Stryker, M. P. (2000). Rapid extragranular plasticity in the absence of thalamocortical plasticity in the developing primary visual cortex. Science, 287, 2029–2031. Wang, X.-F., Jin, X.-T., & Daw, N. W. (1998). The effect of ACPD on the responses to NMDA and AMPA varies with layer in slices of rat visual cortex. Brain Research, 812, 186–192. Wang, X.-F., & Daw, N. W. (2003). Long-term potentiation varies with layer in rat visual cortex. Brain Research, 989, 26–34. Yoshimura, Y., Ohmura, T., & Komatsu, Y. (2003). Two forms of synaptic plasticity with distinct dependence on age, experience, and NMDA receptor subtype in rat visual cortex. Journal of Neuroscience, 23, 6557–6566.