Granular Cells of the Mormyrid Electrosensory Lobe and Postsynaptic Control Over Presynaptic Spike Occurrence and Amplitude Through an Electrical Synapse

Primary afferent fibers from the electroreceptors of mormyrid electric fish use a latency code to signal the intensity of electrical current evoked by the fish's own electric organ discharge (EOD). The afferent fibers terminate centrally in the deep and superficial granular layers of the electrosensory lobe with morphologically mixed chemical–electrical synapses. The granular cells in these layers seem to decode afferent latency through an interaction between primary afferent input and a corollary discharge input associated with the EOD motor command. We studied the physiology of deep and superficial granular cells in a slice preparation with whole cell patch recording and electrical stimulation of afferent fibers. Afferent stimulation evoked large all-or-none electrical excitatory postsynaptic potentials (EPSPs) and large all or none GABAergic inhibitory postsynaptic potentials (IPSPs) in both superficial and deep granular cells. The amplitudes of the electrical EPSPs depended on postsynaptic membrane potential, with maximum amplitudes at membrane potentials between −65 and −110 mV. Hyperpolarization beyond this level resulted in either the abrupt disappearance of EPSPs, a step-like reduction to a smaller EPSP, or a graded reduction in EPSP amplitude. Depolarization to membrane potentials lower than that yielding a maximum caused a linear decrease in EPSP amplitude, with EPSP amplitude reaching 0 mV at potentials between −55 and −40 mV. We suggest that the dependence of EPSP size on postsynaptic membrane potential is caused by close linkage of pre- and postsynaptic membrane potentials through a high-conductance gap junction. We also suggest that this dependence may result in functionally important nonlinear interactions between synaptic inputs.

Intracellular Analysis of Reflex Pathways Underlying the Stumbling Corrective Reaction During Fictive Locomotion in the Cat

In cat and humans, contact between an obstacle and the dorsum of the foot evokes the stumbling corrective reaction (reflex) that lifts the foot to avoid falling. This reflex can also be evoked by short trains of stimuli to the cutaneous superficial peroneal (SP) nerve in decerebrate cats during the flexion phase of fictive locomotion. Here we examine intracellular events in hindlimb motoneurons accompanying stumbling correction. SP stimulation delivered during the flexion phase excites knee flexor motoneurons at short latency [minimum excitatory postsynaptic potential (EPSP) latency 1.8 ms; mean 2.7 ms]. Although a similar short latency excitation occurs in ankle extensors (mean latency, 2.8 ms), recruitment is delayed until successive shocks in the stimulus train overcome the locomotor-related hyperpolarization of ankle extensors. In ankle flexor motoneurons, SP stimulation evokes an inhibition (mean latency, 2.7 ms) that briefly reduces or stops their firing during the flexion phase. There is a phase-dependent modulation of SP-evoked EPSP amplitude as well as latency during locomotion. However, the more obvious change in SP reflex pathways with the onset of fictive locomotion is the reduced inhibition of ankle extensor motoneurons and the increased inhibition of ankle flexors. These results show that the characteristic pattern of hindlimb motoneuron activation during SP nerve–evoked stumbling correction results from 1) di- and trisynaptic excitation of knee flexor and ankle extensor motoneurons; 2) increased inhibitory postsynaptic potentials in ankle flexors and a suppression of inhibition in extensors, 3) sculpting of the short-latency SP postsynaptic effects by motoneuron membrane potential, and 4) longer latency excitatory effects that are likely evoked by lumbar interneurons involved in the generation of fictive locomotion.

Stimulus-Evoked Modulation of Sensorimotor Pyramidal Neuron EPSPs

Sensory cortical neurons display substantial receptive field dynamics during and after persistent sensory drive. Because a cell's response properties are determined by the inputs it receives, receptive field dynamics are likely to involve changes in the relative efficacy of different inputs to the cell. To test this hypothesis, we have investigated if brief repetitive stimulus drive in vitro alters the efficacy of two types of corticocortical inputs to layer V pyramidal cells. Specifically, we have used whole cell recordings to measure the effect of repetitive electrical stimulation at the layer VI/white matter (WM) border on the synaptic response of layer V pyramidal cells to corticocortical input evoked by electrical stimulation of layer I or layer II/III and emulated by local application of glutamate. Repetitive stimulation (10 Hz for 3 s) at the layer VI/WM border transiently potentiated excitatory postsynaptic potentials (EPSPs) evoked by electrical stimulation of layer II/III by 97 ± 12% (mean ± SE). The recovery of EPSP amplitude to its preconditioning value was well-described by a single-term decaying exponential with a time constant of 7.2 s. The same layer VI/WM conditioning train that evoked layer II/III EPSP potentiation frequently caused an attenuation of layer I EPSPs. Similarly, subthreshold postsynaptic responses to local glutamate application in layers II/III and I were potentiated and attenuated, respectively, by the conditioning stimulus. Potentiation and attenuation could be evoked in the same cell by repositioning the glutamate puffer pipette in the appropriate layer. The conditioning stimulus that led to the transient modification of upper layer EPSP efficacy also evoked a slow depolarization in glial cells. The membrane potential of glial cells recovered with a time course similar to the dissipation of the potentiation effect, suggesting that stimulus-evoked changes in extracellular potassium (ECK) play a role in layer II/III EPSP potentiation. Consistent with this proposal, increasing the bath concentration of ECK caused a substantial increase of layer II/III EPSP amplitude. EPSP potentiation was sensitive to postsynaptic membrane potential and, more importantly, was significantly weaker for synaptic currents than for synaptic potentials, suggesting that it involves the recruitment of a postsynaptic voltage-dependent mechanism. Two observations suggest that layer II/III EPSP potentiation may involve the recruitment of postsynaptic sodium channels: EPSP potentiation was strongly reduced by intracellular application of N-(2,6-dimethyl-phenylcarbamoylmethyl) triethylammonium bromide (QX-314) and responses to local glutamate application were potentiated by high ECK in the presence of cadmium but not in the presence of tetrodotoxin. The results demonstrate a novel way in which brief periods of repetitive stimulus drive are accompanied by rapid, transient, and specific alterations in the functional connectivity and information processing characteristics of sensorimotor cortex.

Dynamic Modulation of Excitation and Inhibition During Stimulation at Gamma and Beta Frequencies in the CA1 Hippocampal Region

Fast oscillations at gamma and beta frequency are relevant to cognition. During this activity, excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs) are generated rhythmically and synchronously and are thought to play an essential role in pacing the oscillations. The dynamic changes occurring to excitatory and inhibitory synaptic events during repetitive activation of synapses are therefore relevant to fast oscillations. To cast light on this issue in the CA1 region of the hippocampal slice, we used a train of stimuli, to the pyramidal layer, comprising 1 s at 40 Hz followed by 2–3 s at 10 Hz, to mimic the frequency pattern observed during fast oscillations. Whole cell current-clamp recordings from CA1 pyramidal neurons revealed that individual stimuli at 40 Hz produced EPSPs riding on a slow biphasic hyperpolarizing-depolarizing waveform. EPSP amplitude initially increased; it then decreased concomitantly with the slow depolarization and with a large reduction in membrane resistance. During the subsequent 10-Hz train: the cells repolarized, EPSP amplitude and duration increased to above control, and no IPSPs were detected. In the presence of GABAA receptor antagonists, the slow depolarization was blocked, and EPSPs of constant amplitude were generated by 10-Hz stimuli. Altering pyramidal cell membrane potential affected the time course of the slow depolarization, with the peak being reached earlier at more negative potentials. Glial recordings revealed that the trains were associated with extracellular potassium accumulation, but the time course of this event was slower than the neuronal depolarization. Numerical simulations showed that intracellular chloride accumulation (due to massive GABAergic activation) can account for these observations. We conclude that synchronous activation of inhibitory synapses at gamma frequency causes a rapid chloride accumulation in pyramidal neurons, decreasing the efficacy of inhibitory potentials. The resulting transient disinhibition of the local network leads to a short-lasting facilitation of polysynaptic EPSPs. These results set constraints on the role that synchronous, rhythmic IPSPs may play in pacing oscillations at gamma frequency in the CA1 hippocampal region.

Electrophysiological Properties and Synaptic Responses of Cells in the Trigeminal Principal Sensory Nucleus of Postnatal Rats

In the rodent brain stem trigeminal complex, select sets of neurons form modular arrays or “barrelettes,” that replicate the patterned distribution of whiskers and sinus hairs on the ipsilateral snout. These cells detect the patterned input from the trigeminal axons that innervate the whiskers and sinus hairs. Other brain stem trigeminal cells, interbarrelette neurons, do not form patterns and respond to multiple whiskers. We examined the membrane properties and synaptic responses of morphologically identified barrelette and interbarrelette neurons in the principal sensory nucleus (PrV) of the trigeminal nerve in early postnatal rats shortly after whisker-related patterns are established. Barrelette cell dendritic trees are confined to a single barrelette, whereas the dendrites of interbarrelette cells span wider territories. These two cell types are distinct from smaller GABAergic interneurons. Barrelette cells can be distinguished by a prominent transient A-type K+ current ( I A) and higher input resistance. On the other hand, interbarrelette cells display a prominent low-threshold T-type Ca2+ current ( I T) and lower input resistance. Both classes of neurons respond differently to electrical stimulation of the trigeminal tract. Barrelette cells show either a monosynaptic excitatory postsynaptic potential (EPSP) followed by a large disynaptic inhibitory postsynaptic potential (IPSP) or just simply a disynaptic IPSP. Increasing stimulus intensity produces little change in EPSP amplitude but leads to a stepwise increase in IPSP amplitude, suggesting that barrelette cells receive more inhibitory input than excitatory input. This pattern of excitation and inhibition indicates that barrelette cells receive both feed-forward and lateral inhibition. Interbarrelette cells show a large monosynaptic EPSP followed by a small disynaptic IPSP. Increasing stimulus intensity leads to a stepwise increase in EPSP amplitude and the appearance of polysynaptic EPSPs, suggesting that interbarrelette cells receive excitatory inputs from multiple sources. Taken together, these results indicate that barrelette and interbarrelette neurons can be identified by their morphological and functional attributes soon after whisker-related pattern formation in the PrV.