Short-Term Regulation of Information Processing at the Corticoaccumbens Synapse

Tonic short-term plasticity direction depends on initial presynaptic release probability. A, In a given neuron, increasing stimulation frequency from 0.2 to 1 Hz led to facilitation of EPSCs in low release probability conditions (extracellular Ca²⁺, 0.5 mm) and to depression in high release probability conditions (extracellular Ca²⁺, 4 mm). B, Average facilitation or depression obtained for six neurons in the two release probability conditions. Error bars indicate SE. C, The extent of changes in EPSC amplitude during tonic short-term plasticity strongly correlated with the initial CV value (measured before shifting frequency to 1 Hz). D, Sample experiment showing the protocol used to determine the relationship between frequency modulation of evoked EPSC amplitude and initial release probability. Frequency modulation was first determined in 2 mm extracellular Ca²⁺ (depression in this example). EPSC amplitude means and variances were subsequently measured in various release probability conditions (here, 0.5 and 4 mm extracellular Ca²⁺, both leading to a decrease in EPSC amplitude variance). E, From the experiment shown in D, variances were plotted as a function of EPSC mean amplitude for each extracellular Ca²⁺ condition and fitted with a parabola of the following equation: y =–(QP/μ)x² + Q(1 + CV²)x, where Q is the weighted averaged quantal response, and CV, μ, and P are the coefficient of variation, the mean amplitude, and the probability of release in 2 mm Ca²⁺ conditions, respectively (Clements, 2003). In the sample experiment shown here, Q = 22 pA, CV = 1.08, μ = 107 pA, and P = 0.704. F, EPSC amplitude changes induced by increasing frequency stimulation from 0.2 to 1 Hz were plotted as a function of initial probability of release for all cells tested. Data points were fitted with a linear regression (r =–0.63).

Burst conditioning of cortical afferent fibers induces positive rebound of excitatory synaptic transmission. A, EPSCs evoked by a conditioning burst of six cortical stimuli (intraburst frequency, 12.5 Hz) and by single test stimuli at variable time intervals after the end of the burst (average of 30 traces). Single bursts of cortical stimulation induced a positive rebound of synaptic transmission independently of the direction of intraburst short-term plasticity (top traces, depression; bottom traces, facilitation). B, Time course for increased EPSC amplitude induced by a burst of stimuli. Mean increase in EPSC amplitude is expressed as a percentage of the amplitude of the first EPSC in the conditioning burst. The rebound was maximal at 5–10 s and recovered to control values 40 s after the end of the burst. Error bars indicate SE.

Repetitive bursts of cortical stimulation induce short-term synaptic plasticity in NAc neurons (RB-STP). A, Repetitive bursts of cortical stimuli induced a cumulative increase in the amplitude of the first EPSC of the burst (filled circle), compared with control EPSCs evoked at a frequency of 0.1 Hz (open circle). Maximal increase in synaptic transmission was reached after 5–10 repetitive bursts and recovered 2–10 min after the end of the burst stimulation protocol. B, Repetitive burst stimulations led to decreased PPR in parallel with an increase in EPSC amplitude. Sample traces of paired EPSCs at the first (left) and the last train (right) of the repetitive burst protocol are shown (inset). C, The amplitude of RB-STP strongly depended on intervals between the successive bursts. RB-STP was maximal for burst repetition each 5 s (mean change, 145 ± 11%; n = 11) and decreased with increasing the inter-burst interval. No synaptic facilitation was observed with bursts separated by 40 s (mean change, 101 ± 5%; n = 11). Error bars indicate SE.

RB-STP involves regulation of K⁺ channels but not Ca²⁺ influx. A, Mean change in the amplitude of EPSCs induced by RB-STP was not affected by changing extracellular Ca²⁺ concentration (0.5, 2, or 4 mm) or by buffering presynaptic Ca²⁺ (BAPTA-AM; 50 μm). RB-STP was not inhibited by the K⁺-channel blockers TEA (10 mm), margatoxin (100 nm), and tityustoxin (100 nm). B, Pretreatment of the slices with 4-AP (100 μm) abolished RB-STP (24 consecutive bursts; 5 s interval; averaged every 15 s; filled circles). Sample average EPSCs recorded during control (left), repetitive bursts (center), and recovery (right) periods are shown (inset). C, Dose–response curve for 4-AP inhibition of RB-STP revealed an IC₅₀ value of 23 μm. Error bars indicate SE.

K⁺ channels regulate afferent axonal excitability in response to repetitive bursts of antidromic stimuli. A, Electrophysiological identification of intrinsic bursting neurons in the PFC displaying a characteristic depolarizing afterpotential (left; black arrow) and a spike doublet at the beginning of the discharge. The current injected through the patch pipette is indicated under each trace. B, Sample of 10 successive antidromic action currents evoked in intrinsic bursting neurons by bipolar stimulation in the NAc during low-frequency stimulation (0.1 Hz) (left) and repetitive bursts (right). B–E, In all experiments with recordings of antidromic action potentials, electrical stimulation was adjusted to obtain a low success rate in control conditions (in the range between 20 and 40%). This allowed us to monitor a potential increase in success rate after RB-STP protocol or acute application of 4-AP. C, Average success rate of antidromic action currents increased during repetitive burst stimulations (filled circle) compared with single control stimulations (open circle). D, This effect was mimicked by bath application of 4-AP (100μm) (4 min). E, In the continuous presence of 4-AP (100μm), repetitive burst stimulations (black circle) did not induce an increase in antidromic success rate. Error bars indicate SE.

RB-STP induces a decrease in EPSC failures without changes in synaptic potency. A, Sample experiment in which cortical fiber stimulation intensity was adjusted to obtain ∼50% of EPSCs but all with similar amplitudes. In these minimal stimulation conditions, RB-STP induces a decrease in the number of failures but EPSCs remained all in the same range of amplitude (i.e., synaptic potency remained constant). The frequency of stimulation was 0.2 Hz, and controls were performed to ascertain that decreasing and increasing stimulation intensity led to failures only and increased synaptic potency, respectively. B, Percentage of EPSC failures under minimal stimulation conditions before (control), during (RB-STP), and after (recovery) RB-STP, for each of the nine cells tested. C, Mean EPSC potencies under minimal stimulation conditions before (control), during (RB-STP), and after (recovery) RB-STP, for each of the nine cells tested.