Research reportLong term potentiation varies with layer in rat visual cortex
Introduction
Several investigators have suggested that LTP and LTD represent early changes which lead on to ocular dominance plasticity and other synaptic alterations that underlie amblyopia [4], [11], [39]. However, the correlation between LTP, LTD and ocular dominance plasticity is not close in the experiments that have been done so far. Application of PKG inhibitors abolishes LTP but not LTD or ocular dominance plasticity [5], [30]. Knockout of the RIIβ subunit of protein kinase A [15] and knockout of the GABA synthesizing enzyme GAD65 [7], [20] impairs LTD and ocular dominance plasticity but not LTP. LTD and some forms of LTP are absent but ocular dominance plasticity is present in mice mutant for the RIβ subunit of protein kinase A [21]. LTD is absent and ocular dominance plasticity is present in mice mutant for the metabotropic glutamate receptor mGluR2 [36]. The only consistent result comes with antagonists for NMDA receptors [2], [10] and protein kinase A inhibitors [5], [30] where LTP, LTD and ocular dominance plasticity are all abolished.
Nearly all these experiments have been done with field potentials recorded in layers II/III and LTP and LTD produced with stimulation of layer IV. We suggest that the lack of correlation may occur because ocular dominance plasticity is measured by recording cells in all layers, and that there are different mechanisms for plasticity in different layers.
Certainly the critical period for plasticity in the visual cortex varies with layer. It has been known for some time that extragranular layers (layers II, III, V and VI) remain plastic for longer than layer IV [9], [34], [38]. More recently, initial changes from monocular deprivation have been shown to occur in layers II and III before those in layer IV [41]. It seems reasonable from this that there should be different mechanisms in different layers.
There are several types of LTP in the visual cortex, which may be NMDAR-dependent, mGluR-dependent or voltage-sensitive calcium channel dependent. Elicitation of LTP depends on an increase of intracellular calcium concentration, which is mediated by calcium influx into postsynaptic neurons either through NMDAR gated ion channels [1], [26], [27], [45], or through voltage-sensitive calcium channels [17], and can also depend, under some conditions, on the release of calcium from inositol triphosphate (IP3)-sensitive stores via the activation of mGluRs [22].
Most previous studies of LTP in visual cortex have been conducted in layer II/III with field potential recordings. Not many of them have used intracellular or whole cell recording techniques, and none have compared recordings in the various layers. Artola and Singer [1] recorded intracellularly in different layers but did not notice any variations. Komatsu and Yoshimura [29] recorded intracellularly in layer V, but did not look at other layers. Dudek and Friedlander [12] recorded intracellularly in layer IV, but did not look at other layers. Our study was started with the hope that different mechanisms would be found for LTP in different layers, and that the results could be used to predict different mechanisms for ocular dominance plasticity in different layers.
According to studies in our laboratory, the distribution of mGluRs varies with layer of visual cortex. In particular, group I mGluRs, which are excitatory, are predominantly expressed on postsynaptic neurons in deeper layers [23], [43], [44]. From this, we hypothesize that mGluR group I-dependent LTP may be induced in deeper layers of visual cortex. Because field potential recordings do not have the required spatial resolution and can only collect data from a group of cells, which may spread to cross the border between the layers of visual cortex, we tested for different mechanisms in different layers by measuring LTP on a single neuron in a specific layer using whole cell recording techniques. In this way, cells can be held at a stable resting potential and constant input resistance for hours in the presence of different specific antagonists for different receptors. As in our previous work on the role of metabotropic glutamate receptors in the responses of cells in various layers of visual cortex [23], we stimulated according to the primary flow of information in the cortex, which is from white matter to layer IV, then to layers II and III, then to layers V and VI [32].
Section snippets
Materials and methods
Rats (16–25 days) were decapitated under halothane anesthesia. The brain was rapidly removed and attached to a platform with superglue and kept in a 2–4 °C cutting solution consisting of (in mM) 215 sucrose, 2.5 KCl, 2.8 MgCl2 1.0 NaH2PO4, 10.0 glucose, 26.2 NaHCO3 and 1.0 CaCl2 at pH 7.3 when equilibrated with 95% O2–5% CO2. Coronal slices of 400 μm thickness were cut using a vibroslicer (World Precision Instruments, Sarasota, FL, USA) and incubated at room temperature for 2 h in an interface
Results
Visually identified, whole-cell recordings were used to record EPSPs from 90 single postsynaptic cells in various layers of the rat visual cortex. These were all pyramidal cells in extragranular layers, as identified in the DIC system as they were being patched. We initially used relatively small synaptic stimulating currents to find a threshold for reliably eliciting stable EPSPs, then quickly made an input–output curve from a minimum EPSP to a saturated one. We used about 1.5× threshold
Discussion
These results show that LTP was induced in various layers of the rat visual cortex, but the mechanism for LTP was different from layer to layer during early development, before the peak of the critical period for plasticity in the visual cortex. The fact that we found differences is surprising, given that we tested a limited fraction of the vast number of connections to be found in the cortex, and that the pyramidal cells that we recorded is not a homogeneous group of cells. There was
Acknowledgements
This work was supported by Public Health Services Grant R01 EY 11353. Nigel Daw is a Senior Scientific Investigator of Research to Prevent Blindness. We thank Mark Yeckel for comments on the manuscript.
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2012, Neuroscience LettersCitation Excerpt :This form of LTP (LTPWM-III) is produced in visual cortex layers II/III by fast frequency, theta-burst stimulation (TBS) of the white matter (WM) below V1 that carries visual information from lateral geniculate nucleus (LGN) to cortical processing areas. Shifts in LTPWM-III production and ocular dominance following arrested visual input during the CP appear to depend upon NMDA receptors [2], metabotropic glutamate receptors [39], and several neurotrophic factors, including brain-derived neurotrophic factor (BDNF) [17,22,26]. After P30, WM stimulation alone seldom evokes LTPWM-III [21,30].