Characteristics of Hippocampal Primed Burst Potentiation in Vitro and in the Awake Rat

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Characteristics of Hippocampal Primed Burst Potentiation in Vitro and in the Awake Rat The Journal of Neuroscience, November 1988, 8(11): 4079-4088 Characteristics of Hippocampal Primed Burst Potentiation in vitro and in the Awake Rat D. M. Diamond, T. V. Dunwiddie, and G. M. Rose Medical Research Service, Veterans Administration Medical Center, and Department of Pharmacology, University of Colorado Health Sciences Center, Denver, Colorado 80220 A pattern of electrical stimulation based on 2 prominent (McNaughton, 1983; Lynch and Baudry, 1984; Farley and Al- physiological features of the hippocampus, complex spike kon, 1985; Byrne, 1987). Of these, a phenomenontermed long- discharge and theta rhythm, was used to induce lasting in- term potentiation (LTP) has received extensive attention be- creases in responses recorded in area CA1 of hippocampal causeit sharesa number of characteristicswith memory. For slices maintained in vitro and from the hippocampus of be- example, LTP has a rapid onset and long duration and is having rats. This effect, termed primed burst (PB) potentia- strengthenedby repetition (Barnes, 1979; Teyler and Discenna, tion, was elicited by as few as 3 stimuli delivered to the 1987). In addition, the decay of LTP is correlated with the time commissural/associational afferents to CAl. The patterns courseof behaviorally assessedforgetting (Barnes, 1979; Barnes of stimulus presentation consisted of a single priming pulse and McNaughton, 1985). The similarity of LTP and memory followed either 140 or 170 msec later by a high-frequency has fostered an extensive characterization of the conditions un- burst of 2-10 pulses; control stimulation composed of un- derlying the initiation of LTP, as well as its biochemical sub- primed high-frequency trains of up to 10 pulses had no en- strates (Lynch and Baudry, 1984; Wigstrijm and Gustafsson, during effect. Of all intervals tested, only 140 and 170 msec 1985a, b; Collingridge and Bliss, 1987). delays between the priming and burst stimuli were effective. Despite this progress,little attention hasbeen directed toward PB potentiation could be induced both homo- and hetero- the issue of how long-term changesin synaptic strength can synaptically. In the latter case, the priming pulse and burst occur as a function of behavioral learning. Recent findings have stimuli were delivered to different dendritic fields; under these led to a partial resolution of this issue.Sharp et al. (1985, 1987) conditions, the PB effect was confined to the “burst” path- showedthat exposure of rats to a novel environment resultsin way. PB potentiation is not dependent on somal spiking; an LTP-like increasein the effectivenessof electrical stimulation dendritic activation appears to be both necessary and suf- of the hippocampus. Similarly, others have shown that an en- ficient for lasting changes to occur. Two findings indicate hancement of synaptic transmission is correlated with behav- that PB potentiation and LTP have common mechanisms: (1) ioral associative learning (Jaffard and Jeantet, 1981; Weisz et The effects of PB stimulation and LTP were not additive, in al., 1984). The basisfor these changesin responsesmay be that that saturation of the enhancement by PB stimulation elim- endogenouspatterns of hippocampal neuronal activity that oc- inated any further increases in response with LTP stimula- cur during learning can activate mechanismsof memory for- tion; and (2) both PB potentiation and LTP were prevented mation. if the N-methyl-D-aspartate antagonists 2-amino&phos- Our approach to testing this hypothesis was through the use phonovaleric acid or phencyclidine were added to the in vitro of electrical stimulation that mimics endogenouspatterns of perfusion medium. Recordings from the hippocampus of hippocampal activity known to occur in behaving animals.Two awake rats demonstrated that PB potentiation of the CA1 such endogenouspatterns are complex spike activity, which is population spike and slope of the EPSP are reliably induced composedof brief high-frequency bursts of 2-5 spikes(Ranck, under physiological conditions. This extensive characterira- 1973; Suzuki and Smith, 1985) and theta rhythm, a 4-12 Hz tion of PB stimulation provides novel information regarding cyclic fluctuation of hippocampal unit (Rose, 1983) and slow the physiological and pharmacological basis of a possible wave (Vanderwolf, 1969; Buzsaki et al., 1983; Bland, 1986) role of endogenous rhythms in the processing and storage activity. Previously, we demonstrated that patterned stimula- of information. tion that mimicked the temporal componentsof complex spike bursting and theta rhythm resulted in a marked reduction in Several forms of synaptic plasticity that may play a role in the threshold for inducing lasting changesin synaptic strength processesunderlying learning and memory have been described (Rose and Dunwiddie, 1986). The patterned stimulation con- in both the vertebrate and invertebrate nervous systems sistedof a singlepriming pulse followed 170 mseclater (i.e., at a theta frequency of 6 Hz) by a high-frequency burst of pulses. Received Nov. 17, 1987; revised Mar. 7, 1988; accepted Apr. 1, 1988. This effect, termed primed burst (PB) potentiation, can be re- This work was supported by the Veterans Administration Medical Research liably evoked in the in vitro CA1 field by only 5 patterned pulses Service, NIDA Grant DA02702, and an ADMH Training Grant to D.M.D. We (Roseand Dunwiddie, 1986).Similar effectsinvolving patterned wish to thank Catherine Bennett for helpful criticism of the manuscript. Correspondence should be addressed to G. M. Rose, Ph.D., Medical Research stimulation and hippocampal synaptic plasticity have been ob- (151), VAMC, 1055 Clermont St., Denver, CO 80220. served in stratum radiatum of CA1 in the awake rat (Staubli Copyright 0 1988 Society for Neuroscience 0270-6474/88/l 14079-10$02.00/O and Lynch, 1987) and in vitro (Larson and Lynch, 1986; Larson 4080 Diamond et al. l Primed Burst Potentiation et al., 1986), as well as in the dentate gyrus of anesthetized rats clipped and a longitudinal incision made. The skull was cleared of (Greenstein et al., 1988). connective tissue and leveled, and holes were drilled for support screws, ground and stimulator indifferent sites, and a microdrive base. The In the present study, we have provided an extensive char- electrical ground consisted of a pair of 250-pm-diameter, Teflon-cov- acterization of PB potentiation. First, we performed parametric ered stainless steel wires from which the insulation had been removed analyses of physiological characteristics of PB potentiation in from the last 3 mm from the tips. The uninsulated portions of these the GA 1 cell body layer of the in vitro hippocampal slice. These wires were placed into the prefrontal cortex bilaterally. (Coordinates, from bregma, were AP +2.0 mm, ML 1.0 mm.) The stimulator indif- experiments identified novel features of PB potentiation, such ferent electrode, a 125 pm stainless steel wire insulated except at the as its threshold and the necessityof dendritic activation, rather tip, was placed in the left cortex (AP -6.0 mm, ML 2.0 mm). than somal spiking, to elicit lasting effects. Second, pharma- The recording site was located over the right dorsal hippocampus (AP cological and physiological manipulations determined that PB -4.2 mm, ML 2.5 mm). The stimulating electrode (125 pm stainless potentiation appearsto be induced through the same mecha- steel wire insulated except at the tip) was aimed at the ventral hippo- campal commissure on the left side (AP - 1.8 mm, ML 1.0 mm). The nismsas conventionally induced LTP. Finally, we demonstrated dura was reflected over each site. A microdrive (Deadwyler et al., 1979) that PB potentiation can be induced in the hippocampusof the fitted with a tungsten microelectrode (impedance 0.7-1.0 Mfl at 1 kHz) awake rat. The findings are discussedin the context of current was nositioned over the recording site, and the electrode was lowered theoriesof LTP and associative learning and the role of endog- into ihe CA1 pyramidal cell laye; The stimulating electrode was then enous patterns of hippocampal activity in the generation of lowered into the commissural pathway. Final stimulator placement was determined by optimizing the amplitude of the population spike re- learning-inducedsynaptic strengthening. corded in response to commissural stimulation (l-l 0 V, 160 msec du- ration pulses). Following this procedure, the recording electrode and microdrive were removed, leaving the microdrive base; the base, as well Materials and Methods as the stimulating, indifferent, and ground electrodes were then ce- mented in place using dental acrylic. Connecting leads from the elec- In vitro preparation trodes were gathered into a socket made using a Cannon ITT Centi-lot The subjects were male Sprague-Dawley albino rats (Harlan Labora- plastic strip. This socket was also cemented to the skull. tories, Indianapolis, IN) weighing 100-200 gm. Following decapitation, Experimentalprocedure. Animals were allowed at least 7 d to recover the hippocampi were dissected free, while the brain was chilled at O- from surgery. Recordings were never made from a rat until its preop- 4°C in a medium containing 124 mM NaCl, 4.9 mM KCl, 1.2 mM erative body weight had been reestablished. All recording was done in KH,PO,, 2.5 mM CaCl,, 2.4 mM MgSO,, 26 mM NaHCO,, and 10 mM a Plexiglas enclosure (2 1 x 22 cm) placed in a sound-attenuating cham- glucose that had been equilibrated with a 95% 0,/5% CO, gas mixture. ber. On the day before testing, a microdrive loaded with a tungsten Transverse slices were cut at 400 pm thickness and transferred to a electrode was reattached to the base cemented on the animal’s skull. A recording chamber (Spencer et al., 1976), where they were kept sub- wire from the recording electrode was plugged into the socket mounted merged in the same medium (warmed to 33.5”C) and perfused at a rate on the rat’s head. The animal was placed in the recording chamber, and of 2 ml/min. a cable into which an FET-operational amplifier (10 x gain) had been Extracellular recordings of field potentials from the CA1 pyramidal built was then also plugged into the head socket.
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