Posttetanic potentiation of the monosynaptic spinal reflex in the cat. A: monosynaptic reflex discharge from gastrocnemius motor neurons in response to a maximum group I afferent volley from gastrocnemius nerve. Control responses (1–4) were followed by a 12‐s tetanus at 555/s, which led to the development of a facilitation of the reflex response (6–8) that persisted for slightly longer than 2 min (b‐i). Test stimuli are presented at 2.4‐s intervals. B: intracellular potentials recorded from biceps semitendinosus motor neuron and generated by single volleys in the biceps semitendinosus nerve. Following a tetanus of 450/s for 15 s, the postsynaptic potential was first depressed for about 0.5–1 s and then potentiated for the next 1.5 min. Test interval in seconds is shown at bottom of each record. The potentiated excitatory postsynaptic potential became large enough to trigger a spike. C: prolonged posttetanic potentiation following 20‐min tetanus. Stimulus was applied to tibial nerve; recordings were obtained from L7 ventral root. •, from left (test) side; ○, from right (control) side which was treated exactly the same as test side except tetanus was omitted. Each plotted point represents an average of 10–20 individual responses. Each test stimulus was delivered at 10‐s intervals. The ordinate refers to degree of potentiation compared to a control value of 1.

Long‐lasting posttetanic potentiation of the hippocampus. A: 1, diagrammatic view of a parasagittal section of the hippocampal formation showing a stimulating electrode placed beneath the angular bundle (ab) to activate perforant pathway fibers (PP) and recording microelectrode in the molecular layer of the dentate area (AD). Hipp Fiss, hippocampal fissure; Stim, stimulatory electrode; Rec, recording electrode; Fim, fimbrial. 2, arrangement of electrodes for concomitant stimulation of experimental pathway and control pathway (in the contralateral hippocampus). B: amplitude of the population excitatory postsynaptic potential (EPSP) for the experimental pathway (•) and ipsilateral control pathway (○) as a function of time and of conditioning trains (15/s for 10 s) indicated by arrows. Each value is a computed average of 30 responses. Values are plotted as a percentage of the mean preconditioning value of the population (POP) EPSP.

Posttetanic potentiation in neuromuscular preparation treated with tetrodotoxin. End‐plate potential (EPP) recorded from a single junction before and after tetanic stimulation applied to the motor nerve terminal. Pulses were 1.0 ms in duration and 3.5 μA in intensity. A: sample records of EPP's before (C) and at indicated intervals (in seconds) after the tetanus at 50/s for 20 s. B: time course of potentiation. Each point represents mean amplitude of 5 posttetanic EPP's and refers to time of the 5th response. Ordinate, average amplitude of posttetanic EPP's as a percentage of control EPP amplitude shown by horizontal line. Control EPP amplitude was computed by averaging about 50 pretetanic responses. Discrepancy between sample records (A) and averaged response (B) is due to the EPP amplitude fluctuation. Temperature was 19°C.

Effects of chronic disuse on synaptic function. A: schematic diagram of the experimental preparation used by Spencer & April 225 to study the effects of disuse (tenotomy) on the synapse between the la afferent fibers and the neurons of Clarke's column nucleus. Interruption of the motor neuron axons (A) by ventral root transection (deefferentation) opens the gamma loop to the tenotomized muscle (B). Note the conventional diagram of the parallel arrangement of intra‐extra‐fusal muscle. In representation of muscle afferents the heavier lines indicate the principal anatomic connections. Dorsal spinocerebellar tract (DSCT) takes its principal connections from the ipsilateral hindlimb group Ia muscle afferents. Ventral spinocerebellar tract (VSCT) takes its principal connections from contralateral hindlimb group Ib muscle afferents. B: monosynaptic (ascending) responses recorded from the acutely transected thoracic spinal cord (1 and 2) and L5 cord dorsum (afferent volley) potential (3 and 4) to single shock stimulation of soleus and gastrocnemius nerves 47 days after unilateral Achilles tenotomy and transection of ventral roots L6, L7, and S1. Traces 1 and 3 are from the operated sides; traces 2 and 4 are from the nonoperated side. Each record consists of 20 superimposed individual responses.

Posttetanic depression. Postsynaptic response in the lateral geniculate following tetanization of the contralateral optic nerve in the cat for 20 s at 500/s (arrow). On the ordinate are plotted the postsynaptic responses relative to control. Subnormality was still present 3 h following the 20‐s tetanus.

Synaptic depression at low rates of stimulation. A: low‐frequency depression in cat monosynaptic spinal reflex. Relation between afferent stimulus frequency and mean monosynaptic reflex output. Stimulus frequency was varied from 0.05/s (3/ min) to 50/s 160. B: low‐frequency depression of a monosynaptic excitatory post‐synaptic potential in cell R2 of the abdominal ganglion of Aplysia produced by stimulating a single fiber in the connective. The steady‐state value of the unitary postsynaptic potential amplitude is plotted as a function of frequency ranging from 1/10 s to 1/s.

Comparison of the plastic capabilities of a chemical and electrical synaptic potential. A: 1, intracellular recording from a cell in chick ciliary ganglion before tetanus. The chemical excitatory postsynaptic potential (EPSP) was reduced in amplitude by adding d‐tubocurarine chloride to bathing solution in a concentration of 5 μg/ml; 2, response recorded 15 s after a tetanus of 50/s was applied to the presynaptic nerve for 20 s; 3–6, response recorded 1, 3, 5, and 10 min after end of tetanus. EPSP is potentiated, whereas electrical synaptic (coupling) potential is unchanged. Cell was hyperpolarized to prevent firing. B: time course of posttetanic potentiation of EPSP in ganglion cell. Measurements of EPSP and electrical coupling potential are expressed as percentage of control amplitude (initial points). Hatched vertical bar shows duration of tetanus (frequency 50/s). EPSP is potentiated by a factor of almost 800%; electrical coupling potential is unchanged.

Heterosynaptic facilitation. A: intracellular recording from cell R2 in Aplysia abdominal ganglion. 1, test excitatory postsynaptic potential (EPSP) produced by stimulation of genital nerve alone; 2, first of 9 pairing trials of test EPSP and response to priming stimulus (6/s train of 1‐s duration to the siphon nerve); 3, seventh pairing trial (note accompanying depolarization and increases in test PSP); 4–8, test PSP 10 s and 3.5, 10, 20, and 30 min after pairing. B: time course of heterosynaptic facilitation. This is the same preparation as in A but a different run. The amplitude of the test EPSP is plotted as a function of time and of pairing; the period of pairing is indicated by arrows. The graph at the bottom indicates the average level of membrane potential in millivolts.

Presynaptic inhibition in Aplysia. Intracellular recording from a red blood cell in the Aplysia abdominal ganglion. 1, complex test excitatory postsynaptic potentials (EPSP's) from the branchial nerve; 2, pairing of test EPSP with a single priming stimulus train (frequency 10/s) to the genital nerve; 3, depression of test EPSP 10 s after priming stimulus; 4–6, recovery of depression during subsequent 4 min.

Postsynaptic mechanism for heterosynaptic facilitation. A: intracellular recordings from the metacerebral cells of the snail. Dynamic current‐voltage curve obtained directly on the oscilloscope. The transients on the positive voltage axis are the lower parts of the action potentials. Zero represents the resting level (49 mV). B: effects of increasing level of membrane potential on the amplitude and configuration of an excitatory postsynaptic potential (EPSP) and an electrotonic potential produced by a square constant current pulse. C: increase in test EPSP produced by stimulating one pathway as a result of a membrane depolarization produced by stimulating another (primary) pathway. The various frames have been aligned to allow reading of changes in membrane potential. 1, test PSP before stimulation of second pathway; 2, first of 7 stimulus trains to a second pathway; 3, fifth stimulus to the second pathway (note depolarization and increase in test PSP); 4–8, decline of amplitude in test PSP with decline of depolarization in the 6.5 min following stimulus to the other nerve. D: detailed changes in test PSP following a pairing experiment similar to that illustrated in C. (Note changes in the test PSP as the membrane potential declines toward the resting level.) Numbers on the left indicate depolarization (in mV) from the resting level.

Synaptic modulations of an endogenously active cell. A: intracellular recordings from cell R15 in the abdominal ganglion of Aplysia. Long‐lasting effects of an excitatory synaptic input (INPUT I). 1, sample record from control 25‐min period to illustrate relative constancy of burst size and interval. 2, sample records during stimulation of input I at 10/s for 4 min. This stimulus produced continuous spiking. 3, sample records from 8 min after stimulation was over, burst size stabilized at 27–29 spikes/burst, and the interburst interval was prolonged. 4, sample records after 4 min of hyperpolarizing the cell to block all spiking. The cell first gave a long train of spikes followed by a return to a burst size of 19–20 spikes, and a return of the interburst interval to the control level. 5, sample record during depolarization with outward current to cause continuous spiking for 4 min, paralleling the spiking caused by the synaptic input in 2. 6, sample record following depolarization illustrated in 5. Depolarization did not cause a subsequent change in burst size, but did cause a prolongation of the interburst interval. Calibration; traces 2 and 5, 0.4 s. B: graphic representation of interburst interval, spike frequency with each burst and burst size as modulated by synaptic input (input I). Left (abscissa in minutesi control period to illustrate synaptic regularity of 3 burst parameters over 3 h. The synaptic input (input I) was then stimulated at 6/s for 3 min after which the abscissa was first expressed as consecutive bursts for 40 bursts and then as time beginning with 0. The synaptic input produces an increase in burst size and frequency. The increase in burst size remains increased for 4 h.

Binocular interaction and plasticity in the cat visual system. A: receptive field of a typical neuron in the cat's left visual cortex (area 17) as mapped for the left (1a) and right (2a) eye. The neuron responds with a train of action potentials to a diagonal bright bar moving to the left. The cell responds more effectively when the stimulus is presented to the contralateral eye (2b) than to the ipsilateral eye (1b), B: on the basis of the responses illustrated in A, Hubel and Wiesel divided the response properties of visual cortical cells into 7 ocular dominance groups. If a cell (small circle) in the right hemisphere is influenced only by the contralateral eye, it falls into group 1. If it receives input only from the ipsilateral eye it falls into group 7. For the intermediate groups, one eye may influence the cell much more than the other (groups 2 and 6) or the differences may be slight (groups 3 and 5). According to these criteria, the cell in A would fall into group 2. C: ocular dominance histograms under different experimental conditions. 1, normal adult cat. Histogram based on 233 cells. 2, kittens monocularly deprived of form vision. Histogram based on 199 cells in 5 kittens 8–14 wk old that had their right eye closed by lid suture from the time of normal eye opening. Shading indicates cells that had the usual specific response properties to visual stimulation. Absence of shading indicates cells that lacked the normal orientation specificity. Interrupted lines indicate cells that did not respond to either eye. 3, kittens raised with experimental squint. Histogram based on 384 cells recorded from 4 animals.

Critical period for monocular deprivation of pattern vision. Ocular dominance histograms based on individual animals deprived of form vision in one (the right) eye for various periods. Numbers on abscissa refer to ocular dominance grouping (see Fig. 12). A: 2 normal, very young, visually inexperienced kittens — one 8 days old and one 16 days old with no previous pattern vision in either eye. B: monocular deprivation from days 9–19. C: monocular deprivation from days 10–31. D: monocular deprivation from days 23–29. E: monocular deprivation from mo 2–3. F: monocular deprivation from mo 4–7. G: a previously normal adult cat monocularly deprived for 3 mo

Critical period for reverse suture. A: ocular dominance histograms in animals with reverse suture following earlier eyelid closure. 1, dominance distribution for control animals monocularly deprived in the right eye until 5 wk. 1–6, results from 5 kittens monocularly deprived in the right (ipsilateral) eye until 5 (2), 6 (3), 8 (4), 10 (5), and 14 (6) wks, respectively, and then reverse sutured. In each case the kitten was then allowed 9 wk of vision using its right (ipsilateral) eye following reverse suturing (left eyelids closed) before recording at the age indicated in parentheses. Numbers on abscissa refer to ocular dominance grouping (see Fig. 12). B: time course of the reversibility of the effects of previous eyelid closure. Reversal index is the ratio of the neurons dominated by the more recently experienced eye (7, 6, and 5) to the total number of visually responsive cells. This index provides an indication of the degree to which the initially deprived eye recaptures the cortex. Broken horizontal line shows the same ratio calculated for the control animals that were monocularly deprived until 5 wk and which had no neurons in groups 7, 6, and 5 (index = 0.0).

Habituation and dishabituation in the acute decerebratespinal preparation. Continuous records of isometric myogram of tibialis anterior under low (<50 g) initial tension. Test stimuli were brief trains (0.5‐s duration) of high frequency (50/s) pulses applied to the skin of the rump at 2‐min intervals. A: 1, habituation and spontaneous recovery. Control rate 1/2 min. Period between arrows indicates response decrement following increase in stimulus frequency to 10/s. Recovery follows after 6 stimuli at the control rate of 1/2 min. 2, restoration of the previously decremented flexion reflex (dishabituation) by introduction of a strong stimulus. Test stimuli were similar to those in 1. Response restoration (during period indicated by shaded rectangle) was produced by a brief pinch to digits of same leg. B: synaptic concomitants of habituation in acute spinal animal. Intracellular recordings of polysynaptic excitatory postsynaptic potential (EPSP) decrement from deep peroneal motor neuron (identified by antidromic activation) in response to single shock stimuli delivered to the superficial peroneal nerve. B: 1, during the control period stimulating rate was 2/min; 2, EPSP decrement during increased stimulation rate at 1‐s intervals; 3, restoration of EPSP amplitude following an extra stimulus delivered to the tibial nerve (tetanus at 100/s for 4‐s duration); 4, subsequent EPSP decrement produced by continued stimulation of 1‐s intervals; 5, spontaneous recovery of PSP amplitude when stimulus rate was restored to 1/2 min. Time and voltage calibration from 1–5, 10 ms and 2 mV.

Responses of two types of interneurons in the cat spinal cord during habituation and sensitization. A: H interneuron. Upper graph represents the amplitude of the flexor twitch of tibial anterior muscle showing slight increase (sensitization) followed by habituation and spontaneous recovery (following rest). Lower graph represents mean number of spikes per stimulus of a simultaneously recorded interneuron. H interneuron shows only a progressive decrease in the evoked discharge even during behavioral sensitization. B: S interneuron. Upper and lower graphs again illustrate flexor twitch of the tibial anterior muscle showing sensitization followed by habituation and spontaneous recovery. Lower graph represents mean number of spikes per stimulus of the simultaneously recorded interneuron. S interneuron shows an initial increase followed by a decrease in evoked discharge. C: schematic diagram of possible neuronal substrate of habituation and sensitization. N, nonplastic synapses; H, habituating synapses; S, sensitizing synapses. According to this scheme, afferent cutaneous stimuli exert their influence on two systems: a reflex system (S‐R) that mediates habituation and a “state” system that mediates sensitization.

Short‐term habituation and dishabituation of the gill‐withdrawal reflex in Aplysia. A: 1, defensive withdrawal reflex of siphon and gill. Dorsal view of an intact Aplysia. The parapodia and mantle shelf have been retracted to reveal the gill. The most sensitive area of the receptive field for eliciting the withdrawal reflex consists of two parts: the rostral edge of the mantle shelf containing the purple gland (dark area) and the caudal edge of the mantle shelf and its continuation as the siphon. The surrounding area is less sensitive. The position of the mantle organs at rest (dotted line) is compared to that during withdrawal reflex following tactile stimulation of the siphon (solid lines). 2, sample photocell records illustrating habituation, spontaneous recovery, and dishabituation of the gill‐withdrawal reflex. The interval between stimuli (ISI) and the total number of habituatory stimuli are indicated. a, decrement of the response with repetition of the stimulus at 3‐min intervals. Following a 122‐min rest, the response was almost fully recovered. b, later experiment from the same preparation. After rehabituation of the response at 1/min, a dishabituatory stimulus consisting of a strong and prolonged tactile stimulus to the neck region was presented at the arrow. Successive responses were facilitated for several minutes. B: central synaptic changes accompanying habituation, recovery, and dishabituation. 1, preparation used to correlate contraction of the gill and responses of motor neuron L7 is similar to that illustrated in A, except that a slit has been made in the neck in order to externalize the abdominal ganglion. To permit intracellular recordings from individual cells, the ganglion, with its nerves intact, has been pinned to a stage. This is illuminated by a light guide. 2–4, the photocell records of the gill contractions are illustrated on the top traces of each line, and the simultaneous intracellular recordings from an identified motor neuron L7 are illustrated on the bottom traces. Sample records are all from the same preparation. Tactile stimuli (500 ms in duration) were presented to the mantle shelf every 90 s. 2, habituation. Stimuli were presented over a period of 21 min. Number of spikes in the 1‐s interval following the first evoked spike in each trace: 9, 6, 6, 4. 3, partial recovery (after a 9‐min rest) and subsequent rehabituation of the reflex. Number of spikes: 7, 6, 5, 3. 4, dishabituation. Following the last habituation trial shown in the first trace, a strong stimulus was applied to the siphon. The discharge of the motor neuron and the amplitude of the gill contraction progressively increased during the first 3 stimuli following the dishabituatory stimulus and remained elevated for several minutes. Number of spikes: 4, 5, 7, 5. C: changes in the elementary monosynaptic excitatory connections between sensory and motor neurons as a result of repetitive stimulation at an interstimulus interval of 1/10 s. 1, experimental setup used to examine elementary connections in the isolated ganglion. Ganglion was bathed in high Mg²⁺ (160 mM) and Ca²⁺ (50 mM) solutions. Sens. N, sensory neuron; M.N., motor neuron. 2–4, Intracellular recording from motor neuron L7 (top trace) and sensory neuron (bottom trace). 2, response decrement of elementary excitatory postsynaptic potential in L7 to 15 repeated stimuli of sensory neuron. Only responses to stimulus numbers 1, 2, 6, 10, and 15 are illustrated. 3, a strong stimulus (6/s train for 4 s) was applied to the connective. This stimulus did not alter the firing pattern of the sensory neuron. 4, following the heterosynaptic stimulus to the connective the amplitude of the elementary EPSP was partially restored.

Estimation of quantal size and quantal content during depression and facilitation of the monosynaptic connection between sensory and motor cells mediating the gill‐withdrawal reflex in Aplysia. Two independent techniques are used: amplitude histogram and failure analysis. A: Amplitude histograms. 200–300 consecutive synaptic responses were obtained by intracellular stimulation of the sensory neuron at 10‐s intervals. The responses were separated into 3 successive plateau regions, each consisting of 30–100 responses in regions of stability in which the EPSP amplitude changed less than 15%. The histograms reveal a peak of failures followed by a multimodal distribution with the mean of each subsequent peak being an integral multiple of the first unit peak. The unit peak was assumed to represent the quantal unit (q). The dotted line and the arrow on the ordinate indicate the theoretical distribution predicted by the Poisson equation. 1, depression. A comparison of the successive regions illustrates that with repeated stimulation the position of the unit peak (I) does not change, but the relative incidence of failures increases 6‐ to 7‐fold from the first to the third region. Thus the 30 stimuli in the first region produced 2 failures, the next 70 stimuli produced 12 failures (or 6 failures for every 35 responses), and the 35 stimuli in the last region produced 14 failures. These findings indicate that the EPSP depression during continued stimulation is due to a decrease in quantal output (in this case m decreased from 4 to 1) while quantal size remains relatively unaffected. 2, facilitation. Synaptic decrement was first produced with 200 consecutive stimuli to the sensory neuron as in 1. The pathway from the head was then stimulated to produce facilitation. The histograms illustrate the last region of depression (prefacilitation region) just before the facilitating stimulus and the 2 regions following the facilitating stimulus (postfacilitation region). In the last region of depression, there are again a large number of failures. Following the facilitating stimulus, the relative number of failures is markedly reduced and changes from 12 failures or 7/33 responses in the first region to 1/33 responses in the next region. But the position of the unit peak again remains the same. Thus, during facilitation, quantal output increases while the size of a quantal unit does not change. B: Failure analysis. Summary of the results on synaptic depression and synaptic facilitation derived by a failure analysis derived from the Poisson equation whereby the quantal content m₀ = lnN/n₀ where m₀ is the quantal content, N is the number of trials and n₀ the number of failures. A first group of 5 experiments was done on synaptic depression and was normalized to the first region prior to facilitation. With both depression and facilitation, the estimated values of quantal size remained constant during successive regions while E, the average excitatory postsynaptic potential amplitude, and m, the quantal content, decreased by 50% during the depression and increased by 100% in relation to the control region during facilitation.

Excitatory postsynaptic potential decrement accompanying habituation in the crayfish. A: lateral giant dendrite responses in the fifth ganglion to repetitive stimulation of the second root of the same segment at 10/s. The 1st, 2nd, 5th, 10th, and 30th responses are shown. The initial downward deflection is the stimulus artifact. The first fast depolarizing potential is an electrotonic component; the slower later wave is the chemically mediated postsynaptic potentials. B: properties of monosynaptic afferent excitatory postsynaptic potentials in tactile interneuron. 1–3, 1st, 4th, and 7th responses to stimulation at 1/5 s. The small late depolarizations are due to occasional activation of tactile afferents whose spikes are not discernible in the root monitor.

Acquisition and retention of long‐term habituation of defensive withdrawal in Aplysia. A: behavioral experiments. Siphon withdrawal is expressed as a percentage of the median of each group's initial response (block 1, trial 1). The median duration of the initial response was 17 s for the experimental and 19 s for the control animals. For statistical analysis, siphon withdrawal for each animal was expressed as a single score: the sum of 10 trials, that is, the total time an animal spent responding in the 10‐trials habituation session. Intergroup statistical comparisons were made with Mann‐Whitney U tests and intragroup comparisons with Wilcoxon matched‐pairs signed‐ranks tests. Following blocks of siphon‐habituation training spaced by 90 min (acquisition), experimental animals (•) exhibited significantly greater habituation (retention) than control animals (○) at 24 h (P < 0.001). B: acquisition and retention of excitatory postsynaptic potential decrement. The EPSP amplitudes from both experimental (•) and control (○) nerves (n = 10) are expressed as a percentage of the initial amplitude. In acquisition, 6 experiments were run with the siphon nerve as experimental. In block 1, 10 stimuli were first applied to the experimental nerve and then to the control nerve, producing in L7 comparable EPSP decrement from both nerves, which indicated lack of EPSP generalization. Repeated blocks of stimuli to the experimental nerve produced progressive buildup of EPSP decrement. A single test to the control nerve produced an EPSP which was recovered to 84.5% control, indicating that deterioration cannot account for experimental EPSP decrement. In retention, the cell was reimpaled 24 h later and repolarized to the membrane potential maintained for acquisition. The ordinate in retention was redrawn to indicate that the repolarization is only closely approximated, it is not exact. In the retention test, stimulation of the experimental nerve produced significantly greater EPSP decrement (P < 0.001) than stimulation of the control nerve. I:b.i., interblock interval; i.t.i., intertrial interval.

Spinal cord conditioning. Mean amplitudes of the response to the conditioned stimulus (CS) alone from 20 animals for test trials in acquisition and during five trial blocks in extinction, given as a percent of mean CS alone.