Facilitation of cortico-amygdala synapses by nicotine: activity-dependent modulation of glutamatergic transmission

The basolateral nucleus of the amygdala (BLA) receives cholinergic innervation from the basal forebrain and nicotine, via activation of neuronal nicotinic acetylcholine receptors (nAChRs), can improve performance in amygdala-based learning tasks. We tested the hypothesis that acute and prenatal nicotine exposure modulates cortico-amygdala synaptic transmission. We found that low-dose, single-trial exposures to nicotine can elicit lasting facilitation, the extent of which is dependent on the level of stimulation of the cortical inputs to the BLA. In addition, sustained facilitation is ablated by prenatal exposure to nicotine. This study examined synaptic transmission in 238 patch-clamp recordings from BLA neurons in acute slice from mouse brain. Pharmacological studies in wild-type and nAChR subunit knock-out mice reveal that activation of presynaptic alpha 7, containing (alpha 7*) and non-alpha 7* nAChRs, facilitates glutamatergic transmission in an activity-dependent manner. Without prior stimulation, application of nicotine elicits modest and transient facilitation of glutamatergic postsynaptic currents (PSCs) in about 40% of BLA neurons. With low-frequency stimulation of cortical inputs nicotine elicits robust facilitation of transmission at about 60% of cortico-BLA synapses and synaptic strength remains elevated at about 40% of these connections for >15 min after nicotine washout. Following paired-pulse stimulation nicotine elicits long-lasting facilitation of glutamatergic transmission at about 70% of cortico-BLA connections. Nicotine reduces the threshold for activation of long-term potentiation of cortico-BLA synapses evoked by patterned stimulation. Prenatal exposure to nicotine reduced subsequent modulatory responses to acute nicotine application.     

Auto-inhibition of rat parallel fibre–Purkinje cell synapses by activity-dependent adenosine release

Adenosine is an important signalling molecule involved in a large number of physiological functions. In the brain these processes are as diverse as sleep, memory, locomotion and neuroprotection during episodes of ischaemia and hypoxia. Although the actions of adenosine, through cell surface G-protein-coupled receptors, are well characterized, in many cases the sources of adenosine and mechanisms of release have not been defined. Here we demonstrate the activity-dependent release of adenosine in the cerebellum using a combination of electrophysiology and biosensors. Short trains of electrical stimuli delivered to the molecular layer in vitro , release adenosine via a process that is both TTX and Ca²⁺ sensitive. As ATP release cannot be detected, adenosine must either be released directly or rapidly produced by highly localized and efficient extracellular ATP breakdown. Since adenosine release can be modulated by receptors that act on parallel fibre–Purkinje cell synapses, we suggest that the parallel fibres release adenosine. This activity-dependent adenosine release exerts feedback inhibition of parallel fibre–Purkinje cell transmission. Spike-mediated adenosine release from parallel fibres will thus powerfully regulate cerebellar circuit output.     

Critical period for activity-dependent elimination of corticospinal synapses in vitro

There is no in vitro model of the critical periods for developmental plasticity, the time windows of plastic changes during development, which may hinder in-depth mechanistic analysis. We have shown previously that the corticospinal tract with synaptic connections can be reconstructed in in vitro co-cultures using slices of the sensorimotor cortex and spinal cord of the rat. In our in vitro system, corticospinal synapses form widely over spinal gray matter during early development, after which those on the ventral side are eliminated in an activity and N-methyl-D-aspartate (NMDA)-dependent manner. A detailed quantitative analysis of the time course of sensitivity to an NMDA blocker was made with this system. Synapse distribution was evaluated by recording field excitatory post-synaptic potentials evoked by deep cortical layer stimulation. Corticospinal axon terminal distribution was examined by anterograde labeling with biocytin. We showed that the D-2-amino-5-phosphonovaleric acid (APV) effect is irreversible for at least the length of culture. When APV was removed from the medium before 6 days in vitro(DIV) or after 11 DIV, elimination of ventral synapses was not blocked. APV sensitivity showed a clearly defined time window. A 6-11 DIV application was necessary and sufficient for the full, irreversible block of synapse elimination. From 6-11 DIV, APV sensitivity seems to decrease gradually but not linearly. This system provides an in vitro model of critical periods for developmental plasticity of central synapses which up to now has not been available.     

Coding of auditory temporal and pitch information by hippocampal individual cells and cell assemblies in the rat

This study reports how hippocampal individual cells and cell assemblies cooperate for neural coding of pitch and temporal information in memory processes for auditory stimuli. Each rat performed two tasks, one requiring discrimination of auditory pitch (high or low) and the other requiring discrimination of their duration (long or short). Some CA1 and CA3 complex-spike neurons showed task-related differential activity between the high and low tones in only the pitch-discrimination task. However, without exception, neurons which showed task-related differential activity between the long and short tones in the duration-discrimination task were always task-related neurons in the pitch-discrimination task. These results suggest that temporal information (long or short), in contrast to pitch information (high or low), cannot be coded independently by specific neurons. The results also indicate that the two different behavioral tasks cannot be fully differentiated by the task-related single neurons alone and suggest a model of cell-assembly coding of the tasks. Cross-correlation analysis among activities of simultaneously recorded multiple neurons supported the suggested cell-assembly model.Considering those results, this study concludes that dual coding by hippocampal single neurons and cell assemblies is working in memory processing of pitch and temporal information of auditory stimuli. The single neurons encode both auditory pitches and their temporal lengths and the cell assemblies encode types of tasks (contexts or situations) in which the pitch and the temporal information are processed.     

Cortical sensory suppression during arousal is due to the activity-dependent depression of thalamocortical synapses

The thalamus serves as a gate that regulates the flow of sensory inputs to the neocortex, and this gate is controlled by neuromodulators from the brainstem reticular formation that are released during arousal. Here we show in rats that sensory-evoked responses were suppressed in the neocortex by activating the brainstem reticular formation and during natural arousal. Sensory suppression occurred at the thalamocortical connection and was a consequence of the activity-dependent depression of thalamocortical synapses caused by increased thalamocortical tonic firing during arousal. Thalamocortical suppression may serve as a mechanism to focus sensory inputs to their appropriate representations in neocortex, which is helpful for the spatial processing of sensory information.     

Coding of temporal parameters of complex sounds by frog auditory nerve fibers

1. Physiological recordings were made from single auditory fibers in the frog eighth nerve to determine quantitatively how the different behaviorally relevant temporal parameters (the signal rise-fall time, duration, and rate of amplitude modulation) of complex sounds are encoded in the auditory periphery. Individual temporal parameters were varied. Response functions (RFs) were constructed with respect to each of these parameters using each unit's best excitatory frequency (BF) as the carrier. 2. In response to a change in signal rise-fall time, auditory nerve fibers showed little change in the mean spike count or firing rate, i.e., all fibers displayed ALL-PASS RFrfts. But the transient components, particularly the early phasic component, of responses varied with rise-fall times; these components were more pronounced in the responses to stimuli with shorter rise-fall times. 3. In response to an increase in signal duration, auditory nerve fibers showed a corresponding increase in firing duration and thus in the mean spike count, giving rise to HIGH-PASS RFdurs. The shape of response curves differed among fibers; the difference appeared to be related to the fiber's temporal adaptation characteristic. When the firing rate was measured, all fibers displayed higher mean firing rates in response to shorter duration stimuli than they did to longer duration stimuli, thus giving rise to LOW-PASS response functions. 4. To determine the response transfer functions to modulation rate, pulsed (PAM) and sinusoidally (SAM) amplitude-modulated signals were used. These signals differed substantially in terms of their envelopes and how they varied with AM rate. Data were analyzed by 1) plotting spike counts against the AM rate to derive modulation transfer functions (MTFspks) and 2) plotting synchronization coefficients (SCs) against the AM rate to generate MTFscs. 5. In response to PAM stimuli, all fibers showed an increase in mean spike count with modulation frequency over the range examined, giving rise to HIGH-PASS MTFspks. 6. For SAM stimuli, the average energy and duty cycle are independent of AM rate. Most (79%) auditory fibers showed little selectivity for AM rate over a range of 5-400 Hz, giving rise to ALL-PASS MTFspks. The remaining auditory fibers displayed LOW-PASS MTFspks, i.e., there was a distinct decline in the mean spike count with increasing AM rate. 7. In response to PAM stimuli, most fibers showed good response synchrony at low AM rates but the SC declined with an increase in the AM rate (i.e., LOW-PASS MTFscs). The cut-off frequency was typically very high, averaging 90 pulses/s.(ABSTRACT TRUNCATED AT 400 WORDS)     

D2-like dopamine receptor-mediated modulation of activity-dependent plasticity at GABAergic synapses in the subthalamic nucleus

Reciprocally connected glutamatergic subthalamic nucleus (STN) and GABAergic external globus pallidus (GP) neurons normally exhibit weakly correlated, irregular activity but following the depletion of dopamine in Parkinson's disease they express more highly correlated, rhythmic bursting activity. Patch clamp recording was used to test the hypothesis that dopaminergic modulation reduces the capability of GABAergic inputs to pattern 'pathological' activity in STN neurons. Electrically evoked GABA(A) receptor-mediated IPSCs exhibited activity-dependent plasticity in STN neurons, i.e. IPSCs evoked at frequencies between 1 and 50 Hz exhibited depression that increased with the frequency of activity. Dopamine, the D(2)-like dopamine receptor agonist quinpirole and external media containing a low [Ca(2+)] reduced both the magnitude of IPSCs evoked at 1-50 Hz and synaptic depression at 10-50 Hz. Dopamine/quinpirole also reduced the frequency but not the amplitude of miniature IPSCs recorded in the presence of tetrodotoxin. D(1)-like and D(4) agonists were ineffective and D(2/3) but not D4 receptor antagonists reversed the effects of dopamine or quinpirole. Together these data suggest that presynaptic D(2/3) dopamine receptors modulate the short-term dynamics of GABAergic transmission in the STN by lowering the initial probability of transmitter release. Simulated GABA(A) receptor-mediated synaptic conductances representative of control or modulated transmission were then generated in STN neurons using the dynamic clamp technique. Dopamine-modulated transmission was less effective at resetting autonomous activity or generating rebound burst firing than control transmission. The data therefore support the conclusion that dopamine acting at presynaptic D(2)-like receptors reduces the propensity for GABAergic transmission to generate correlated, bursting activity in STN neurons.     

Coding of visual information by units in the cat cerebellar vermis

Summary Extracellular records were made of the responses to precisely controlled stationary or moving visual stimuli of 174 units in the cerebellar vermis of cats anaesthetised with chlor alose. Identified Purkinje cells and unidentified units responded similarly. Responses to ON and to OFF steps of a stationary light bar had different characteristics. Some units showed changes in the form of their ON responses related to different positions of the stimulus in their large receptive fields. In some cases changes in response latency from different field positions were also noted. Some units responded only to binocular stimulation and others gave much larger responses to binocular than to monocular stimulation. In addition, some were sensitive to the relative retinal disparity of images and, of these, several were sensitive to vertical as well as to horizontal retinal disparity. Sinusoidally-moving light bars gave responses consisting of one or two bursts of impulses per cycle; the most effective frequency was about 3 Hz. These responses may represent detection of the instant of maximum velocity.The relatively precise coding of retinal disparity in spite of the large size of receptive fields and the coding of position within these large fields is discussed. A possible function for the disparity-sensitive units in the control of vergence is suggested and the relation of this control to visual depth detection and to the estimation of the absolute distance of objects from the animal is discussed.     

The effect of a preceding stimulus on temporal facilitation at corticomotoneuronal synapses

1. Intracellular recordings were made of minimal corticomotoneuronal e.p.s.p.s in lumbar motoneurones of anaesthetized monkeys. For intervals of 2 msec and greater between paired cortical shocks, the average time course of facilitation of the second e.p.s.p. with respect to the first could be fitted closely by a negative exponential with a time constant of 10 msec.2. In the same motoneurones, ;triplets' of corticomotoneuronal e.p.s.p.s were generated by delivering three identical stimuli to the motor cortex. Considering the triplet as a conditioning e.p.s.p. followed by a test pair, the facilitation of the third e.p.s.p. with respect to the second was measured for various combinations of test and conditioning intervals. In each case the amplitude of the third e.p.s.p. was also compared with that of the first (conditioning) e.p.s.p.3. The effect of a brief conditioning interval was to reduce considerably the facilitation of the third e.p.s.p. with respect to the second at all test intervals from 2 to 50 msec. Combinations of brief conditioning intervals (e.g. 2 or 5 msec) and long test intervals (e.g. 20 or 50 msec) caused the third e.p.s.p. to be smaller than the second. As the conditioning interval lengthened, facilitation in the test pair increased towards the unconditioned values at all test intervals.4. Facilitation of the third e.p.s.p. with respect to the first could be described approximately as the linear addition of two facilitation components, one due to the conditioning input and one due to the first stimulus of the test pair. Each component followed the same negative exponential time course as found for an isolated pair of e.p.s.p.s and each of the first two inputs contributed to the facilitation of the third e.p.s.p. as if the other of these two inputs had not occurred.     

Coding of visual information by precisely correlated spikes in the lateral geniculate nucleus

Correlated firing among neurons is widespread in the nervous system. Precisely correlated spiking, occurring on a millisecond time scale, has recently been observed among neurons in the lateral geniculate nucleus with overlapping receptive fields. We have used an information-theoretic analysis to examine the role of these correlations in visual coding. Considerably more information can be extracted from two cells if temporal correlations between them are considered. The percentage increase in information depends on the degree of correlation; the average increase is approximately 20% for strongly correlated pairs. Thus, precise temporal correlation could be used as an additional information channel from thalamus to visual cortex.     

In vitro formation and activity-dependent plasticity of synapses between Helix neurons involved in the neural control of feeding and withdrawal behaviors

Short-term activity-dependent synaptic plasticity has a fundamental role in short-term memory and information processing in the nervous system. Although the neuronal circuitry controlling different behaviors of land snails of the genus Helix has been characterized in some detail, little is known about the activity-dependent plasticity of synapses between identified neurons regulating specific behavioral acts. In order to study homosynaptic activity-dependent plasticity of behaviorally relevant Helix synapses independently of heterosynaptic influences, we sought to reconstruct them in cell culture. To this aim, we first investigated in culture the factors regulating synapse formation between Helix neurons, and then we studied the short-term plasticity of in vitro-reconstructed monosynaptic connections involved in the neural control of salivary secretion and whole-body withdrawal. We found that independently of extrinsic factors, cell-cell interactions are seemingly sufficient to trigger the formation of electrical and chemical synapses, although mostly inappropriate--in their type or association--with respect to the in vivo synaptic connectivity. The presence of ganglia-derived factors in the culture medium was required for the in vitro reestablishment of the appropriate in vivo-like connectivity, by reducing the occurrence of electrical connections and promoting the formation of chemical excitatory synapses, while apparently not influencing the formation of inhibitory connections. These heat-labile factors modulated electrical and chemical synaptogenesis through distinct protein tyrosine kinase signal transduction pathways. Taking advantage of in vitro-reconstructed synapses, we have found that feeding interneuron-efferent neuron synapses and mechanosensory neuron-withdrawal interneuron synapses display multiple forms of short-term enhancement-like facilitation, augmentation and posttetanic potentiation as well as homosynaptic depression. These forms of plasticity are thought to be relevant in the regulation of Helix feeding and withdrawal behaviors by inducing dramatic activity-dependent changes in the strength of input and output synapses of high-order interneurons with a crucial role in the control of Helix behavioral hierarchy.     

Circadian rhythm dissociation in an environment with conflicting temporal information.

The relative contributions of light-dark (LD) cycles and feeding (EF) cycles in providing temporal information to the circadian time-keeping system were examined in chair-acclimatized squirrel monkeys (Saimiri sciureus). The circadian rhythms of drinking, colonic temperature, urine volume, and urinary potassium excretion were measured with the LD and EF cycles providing either conflicting phases or periods. In conflicting phase experiments, animals were exposed to 24-h LD cycles consisting of 12 h of 600 lx followed by 12 h of less than 1 ls and concurrent 24-h EF cycles in which the animals ate for 3 h and then fasted for 21 h. One group had food available at the beginning and a second group at the end of the light period. In conflicting period experiments, monkeys were exposed to 23-h LD cycles (LD 11.5:11.5) and 24-h EF cycles (EF 3:21). Analysis of the rhythms showed that both phase and period information were conveyed to the drinking and urinary rhythms by the EF cycle, and to the temperature rhythm by the LD cycle.     

Ribbon synapses compute temporal contrast and encode luminance in retinal rod bipolar cells

Contrast is computed throughout the nervous system to encode changing inputs efficiently. The retina encodes luminance and contrast over a wide range of visual conditions and must adapt its responses to maintain sensitivity and to avoid saturation. We examined the means by which one type of adaptation allows individual synapses to compute contrast and encode luminance in biphasic responses to step changes in light levels. Light-evoked depletion of the readily releasable vesicle pool (RRP) at rod bipolar cell ribbon synapses in rat retina limited the dynamic range available to encode transient, but not sustained, responses, thereby allowing the transient and sustained components of release to compute temporal contrast and encode mean light levels, respectively. A release/replenishment model revealed that a single, homogeneous pool of synaptic vesicles is sufficient to generate this behavior and that a partial depletion of the RRP is the dominant mechanism for shaping the biphasic contrast/luminance response.     

Combining multisensory temporal information for movement synchronisation

The ability to synchronise actions with environmental events is a fundamental skill supporting a variety of group activities. In such situations, multiple sensory cues are usually available for synchronisation, yet previous studies have suggested that auditory cues dominate those from other modalities. We examine the control of rhythmic action on the basis of auditory and haptic cues and show that performance is sensitive to both sources of information for synchronisation. Participants were required to tap the dominant hand index finger in synchrony with a metronome defined by periodic auditory tones, imposed movements of the non-dominant index finger, or both cues together. Synchronisation was least variable with the bimodal metronome as predicted by a maximum likelihood estimation (MLE) model. However, increases in timing variability of the auditory cue resulted in some departures from the MLE model. Our findings indicate the need for further investigation of the MLE account of the integration of multisensory signals in the temporal control of action.     

Coding of disparity information in extrastriate cortex of the cat

Effective sigma tracking, i.e., apparent movement perception when slow eye movements are made across a stationary repetitive pattern under stroboscopic illumination, has been shown to be a function of the distance between sequential stimuli (P(s)) and the flash frequency (f(s)). The relationship between these factors and eye velocity ( V (e)) has been formally specified as V (e)= k P(s)f(s)[deg s(-1)], where it has been argued that the value of k, which defines the rate limit for eye velocity, is normally 1, or exceptionally 2 or 3. However, theoretically the limitations on the maximum value for k are the maximum optimal pursuit speed for eye tracking (V(max)) and the minimum values which P(s) and f(s) can assume while preserving target discrimination, and since the values for V(max) are known to lie well beyond 20 deg/s and those for P(s) and f s) well below 0.3 deg and 10 Hz respectively, it should be possible to demonstrate empirically that k can assume integer values considerably larger than the indicated maximum of 3. To test this prediction, three subjects performed seven series of five EOG-monitored trials producing sigma-pursuit, with values of k ranging from 1 to 7. All subjects evidenced smooth pursuit eye tracking for every condition and reported experiencing sigma-type apparent motion in 95% of the trials. The results confirm theoretical expectations and unequivocally demonstrate that sigma tracking can be readily effected under conditions where k significantly exceeds the maximal values previously reported, in conformity with theory.     

Models of activity-dependent neural development

Activity-dependent, competitive mechanisms of synaptic plasticity appear to play an important role in many processes of late neural development, where an initially rough connectivity pattern refines to a precise, mature pattern. A prominent example is the formation of ocular dominance columns in the visual cortex of many mammals. These processes may be modeled at several levels. Simple models use abstract neurons and assume synaptic modification according to a hebbian or similar correlation-based rule. These models incorporate biological constraints and attempt to predict large-scale developmental patterns from the combination of synaptic-level plasticity rules and measurable biological patterns of activation and connectivity. More detailed models attempt to incorporate various levels of biophysical realism, including membrane and channel properties and dendritic geometry. Abstract models examine the connectivity patterns that may result if biological development follows certain dynamical or other abstract rules, without concern for how such rules might be implemented at the synapse. The strengths and weaknesses of these approaches are examined through study of models for the development of ocular dominance and of orientation selectivity in the visual cortex.     

Cholinergic synapses of the associative temporal area of the neocortex in the realization of cognitive functions

The activity of choline acetyltransferase in the subsynaptic fractions of light and heavy synaptosomes of the associative temporal areas of the neocortex of cats with varying capacities for the formation of preverbal concepts was investigated. With respect to the majority of the subfractions, differences were detected between animals with normal and decreased intellect. Some theoretical conclusions were drawn relative to the origin of the individual subfractions; the role of cholinergic synapses of the area in question in the realization of the function of generalization and abstraction is discussed. Translated from Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 79, No. 9, pp. 18–25, September, 1993.