Biological information storage events are often rapid transitions between discrete states. In neural systems, the initiation of bidirectional plasticity by all-or-none events may help confer robustness on memory storage. Here, we report that at CA3-CA1 hippocampal synapses, individual potentiation and depression plasticity events are discrete and heterogeneous in nature. Individual synapses began from extreme high and low strength states. Unitary plasticity events were all-or-none and drove synaptic strength between extremes in <1 min. Under naïve conditions, approximately three-fourths of synapses began in a low-strength state. The timing of these unitary events can account for the time course of macroscopic synaptic plasticity.B oth increases (long-term potentiation, LTP) (1) and decreases (long-term depression, LTD) in synaptic strength are almost always measured macroscopically across populations of synaptic contacts (2). Macroscopic recordings, in which plasticity appears as a graded phenomenon, have ranged from extracellular recordings from many thousands of synapses (3, 4) to single-cell recordings (5), including recordings from connected pairs of nearby single neurons representing summed activity from order 10 synaptic terminals (6, 7).Plasticity has been described in terms of transitions among distinct states (7). However, the concept of synaptic states has not been explored in terms of unitary synaptic strength. Characterizing plasticity at this level requires observations from putative single terminals.An attractive system for studying unitary plasticity events is the hippocampal CA3-CA1 pathway (4, 8), where connected CA3 and CA1 neurons communicate typically by a single synaptic contact (9). Minimal stimulation techniques (10-12) allow plasticity transitions to be localized in time as they occur (13). Previous work (13) indicates that unitary synaptic potentiation, at least in its initial stages, may be an all-or-none event.Here, we report on the unitary properties of the initiation of potentiation and depression at CA3-CA1 synapses. We find that both potentiation and depression events are all-or-none and sudden. These events can be reconstituted to account for the time course of plasticity on a macroscopic scale.
MethodsSlice Preparation. Transverse hippocampal slices (300 m) from Sprague-Dawley rats (postnatal day 13-21) were cut in ice-cold artificial cerebrospinal fluid (ACSF) comprising (in mM) 126 NaCl, 3 KCl, 1 NaH 2 PO 4 , 25 D-glucose, 25 NaHCO 3 , 2 CaCl 2 , and 1 MgCl 2 saturated with 95% O 2 ͞5% CO 2 , incubated at 34°C for 10-15 min, and transferred to a room-temperature interface chamber for Ն60 min before recording. The cutting angle was such that excitatory postsynaptic current (EPSC) size in response to stimulation of stratum radiatum decreased rapidly as the stimulation electrode was moved toward CA3. By using this cutting angle and moving the stimulation electrode as far toward CA3 as possible, we reduced the likelihood of stimulating multiple connected axons. For recordings, slic...