Inhibition Of Spike Activity Research Articles

Optogenetic manipulations of preBötC μ‐opioid receptor expressing neurons reveal dual mechanisms of opioid‐induced respiratory depression

The analgesic utility of opiates is limited by the risk for adverse and life‐threatening side effects, including respiratory depression. Opioid‐induced respiratory depression (OIRD) is characterized by a pronounced decrease in the frequency and regularity of inspiratory efforts. The inspiratory rhythm originates from the preBotzinger Compex (preBötC), a region in the ventral medulla that contains neurons that express the μ‐opioid receptor (μOR) and is intrinsically sensitive to opioids, including the synthetic μOR agonist DAMGO. However, the cellular‐level mechanisms of opioid‐induced suppression of rhythmogenesis within the preBötC are controversial. Some evidence suggests opiates regulate synaptic transmission while other evidence suggests membrane potential (Vm) is the primary effector. At the network level, the frequency and regularity of the inspiratory rhythm is primarily determined by the interburst interval IBI which is regulated, in part, by excitatory neurons with “pre‐inspiratory” (pre‐I) spiking activity, but the network‐level effects of opiates have not been well defined. To shed light on these cellular‐ and network‐level processes, we utilized Oprm1Cre mice to optogenetically manipulate μOR neurons in vitro and in vivo. In brainstem slice preparations from Oprm1Arch neonatal mice, unit recordings from pre‐I neurons revealed that 37% of these neurons express μOR. In the presence of increasing concentrations of DAMGO, pre‐I spiking was eliminated initially, followed by suppression of spiking activity during inspiratory bursts. Next, using intracellular recordings, laser power was tuned such that photoinhibition hyperpolarized μOR neurons by ~5–10mV, mimicking the effect of DAMGO on Vm when bath applied at concentrations (100–300nm) that dramatically suppress inspiratory frequency (>90%). However, bilateral photoinhibition of μOR neurons reduced frequency by 36%, only partially mimicking the suppression of frequency by DAMGO. In slices from Oprm1ChR2 mice, photostimuation of μOR neurons under control conditions increased frequency by 204%, indicating that these neurons are integrated within this rhythmogenic network. However, following suppression of the rhythm with DAMGO, ChR2‐mediated depolarization of μOR neurons could not rescue inspiratory frequency. These findings in vitro were largely corroborated by experiments in anesthetized mice in vivo, and suggest that hyperpolarization of μOR neurons at the cellular‐level only partially contributes to OIRD in the preBötC. Based on these initial results, we propose a model of preBötC OIRD in which the effects of opioids are twofold: 1) a modest hyperpolarization of μOR neurons at the cellular‐level reduces pre‐I spiking activity within the network and causes the duration between inspirations to become longer and more irregular, followed by 2) a crash in network‐driven rhythmogenesis, potentially through a μOR‐mediated reduction in the efficacy of excitatory synaptic transmission.Support or Funding InformationK99 HL145004 (Baertsch)R01 HL144801 (Ramirez)

Ectopic Expression of Multiple Microbial Rhodopsins Restores ON and OFF Light Responses in Retinas with Photoreceptor Degeneration

By expressing channel rhodopsin-2 (ChR2) in inner retinal neurons, previous studies have demonstrated restoration of ON responses in the retina after the death of rod and cone photoreceptors. In this study, we report that the expression of halorhodopsin (HaloR), a light-driven chloride pump, can effectively restore OFF responses in inner retinal neurons of mice with retinal degeneration. We show that HaloR-expressing retinal ganglion cells respond to light with rapid hyperpolarization and suppression of spike activity. After termination of the light stimulus, their membrane potential exhibits a rapid rebound overshoot with robust sustained or transient spike firing. Furthermore, we show that coexpression of ChR2/HaloR in retinal ganglion cells can produce ON, OFF, and even ON-OFF responses, depending on the wavelength of the light stimulus. Our results suggest that the expression of multiple microbial rhodopsins such as ChR2 and HaloR is a possible strategy to restore both ON and OFF light responses in the retina after the death of rod and cone photoreceptors.

High frequency stimulation or elevated K + depresses neuronal activity in the rat entopeduncular nucleus

High frequency stimulation (HFS) is applied to many brain regions to treat a variety of neurological disorders/diseases, yet the mechanism(s) underlying its effects remains unclear. While some studies showed that HFS inhibits the stimulated nucleus, others report excitation. In this in vitro study, we stimulated the rat globus pallidus interna (entopeduncular nucleus, EP), a commonly stimulated area for Parkinson’s disease, to investigate the effect of HFS-induced elevation of extracellular potassium (K + e) on rat EP neuronal activity. Whole-cell patch-clamp recordings and [K +] e measurements were obtained in rat EP brain slices before, during and after HFS. After HFS (150 Hz, 10 s), [K +] e increased from 2.5–9.6±1.4 mM, the resting membrane potential of EP neurons depolarized by 11.1±2.5 mV, spiking activity was significantly depressed, and input resistance decreased by 25±6%. The GABA A receptor blocker, gabazine, did not prevent these effects. The bath perfusion of 6 or 10 mM K +, with or without synaptic blockers, mimicked the HFS-mediated effects: inhibition of spike activity, a 20±9% decrease in input resistance and a 17.4±3.0 mV depolarization. This depolarization exceeded predicted values of elevated [K +] e on the resting membrane potential. A depolarization block did not fully account for the K +-induced inhibition of EP neuronal activity. Taken together, our results show that HFS-induced elevation of [K +] e decreased EP neuronal activity by the activation of an ion conductance resulting in membrane depolarization, independent of synaptic involvement. These findings could explain the inhibitory effects of HFS on neurons of the stimulated nucleus.

Comparison Between Offset and Onset Responses of Primary Auditory Cortex on–off Neurons in Awake Cats

Primary auditory cortex (A1) neurons are believed not to carry much information about tonal offsets because A1 neurons in barbiturate-anesthetized animals are usually described as having only onset responses. We investigated tonal offset responses in comparison with onset responses in the caudal part of A1 of awake cats. Cells responding to both onsets and offsets were commonly found (59.2% of recorded cells). Offset responses usually co-occurred with phasic onset responses or phasic components of sustained responses. These ON-OFF cells had diverse combinations of offset- and onset-frequency-receptive field (FRF): offset-FRF was similar to onset-FRF, or narrower, wider, lower, or higher than onset-FRF. The distribution of FRF patterns was diffuse with no boundaries between the different FRF-pattern groups. The onset- versus offset-FRF pattern of each cell remained unchanged across multiple stimulus intensities. Mean offset response showed similar peak latency (19.5 vs. 21.5 ms), longer half-decay time (74.5 vs. 48.5 ms), and lower peak amplitude (20.4 vs. 35.9 spikes/s) compared with the mean onset response. Although offset responses were facilitated when preceded by the suppression of spike activity, they were still elicited without preceding spike suppression. It is concluded that neurons showing paired onset and offset responses are predominant in the caudal A1. Their frequency-filtering property is usually not static but dynamic, changing between sound onsets and offsets. Offset responses are similarly precise and salient as onset responses for effectively encoding sound offsets. They may be elicited as active spike responses to sound offset rather than simple rebound facilitation.

Olfactory sensitivities of mosquitoes with different host preferences ( Anopheles gambiae s.s., An. arabiensis, An. quadriannulatus, An. m. atroparvus) to synthetic host odours

Responses of antennal olfactory cells associated with sensilla trichodea were recorded in females of four Anopheles species (Diptera, Culicidae) with different host preferences: the anthropophilic An. gambiae s.s., the opportunistic An. arabiensis, and the zoophilic An. quadriannulatus and An. maculipennis atroparvus. Stimuli were vapours of synthetic host-odours: ethanoic, propanoic, butanoic, 3-methyl propanoic, 4-methyl butanoic acid, 1-octen-3-ol, and 3- and 4-methyl phenol. On stimulation with fatty acids and phenols either excitation or inhibition of spike activity was found, whereas responses to 1-octen-3-ol were invariably excitatory. The odour spectra of the cells could include activating as well as inhibiting substances. Differences in host preferences may be reflected in the numbers of olfactory cells responding to different odours and/or in the sensitivities of these cells. In An. gambiae more cells were excited by fatty acids than in An. arabiensis and An. m. atroparvus, whereas inhibition occurred more often in the latter two species. In addition, the fatty acid-excited cells in An. gambiae were more sensitive to these substances than in An. m. atroparvus and An. quadriannulatus. On the contrary, in the latter two species cells were more responsive to 1-octen-3-ol. In An. arabiensis, responses of stimulus-excited cells were intermediate between those in the anthropophilic and zoophilic species.

Sensitivity of hippocampal interneurons and pyramidal cells to GABA and some of its agonists:in vitro experiments

Effects of GABA and its agonists baclofen and muscimol on the background spike activity of single hippocampal neurons were studied in rat brain slices using an intracellular recording technique. Interneurons localized in thestratum alveus-oriens and pyramidal neurons of thestratum pyramidale showed high sensitivity to GABA (mean ID50=65 µM and 40 µM, ranges 10–140 µM and 3–200 µM), baclofen (ID50=2.6 µM and 3.5 µM, ranges 0.6–20.0 µM and 0.4–30.0 µM), and muscimol (ID50=0.85 µM and 0.21 µM, ranges 0.11–4.0 µM and 0.05–0.45 µM, respectively). Responses of hippocampal neurons to application of GABA or either of its agonists were predominantly inhibitory. A part of interneurons (30%) differed from pyramidal neurons in their irresponsivity or low sensitivity to baclofen applications. GABA- or muscimol-induced inhibition of spike activity in many pyramidal cells was preceded by a short-lasting excitation. Our findings indicate that a part of hippocampal interneurons are very poorly supplied with GABAb receptors. Inhibition of pyramidal cells evoked by activation of GABAa receptors probably develops against the background of accompanying depolarization, which in some cases can result in a provisional excitation of these neurons. The excitatory effects of GABA on the pyramidal cells are mediated by GABAa receptors.

Bursting electrical activity in pancreatic ?-cells: evidence that the channel underlying the burst is sensitive to Ca2+ influx through L-type Ca2+ channels

In glucose-stimulated pancreatic beta-cells, the membrane potential alternates between a hyperpolarized silent phase and a depolarized phase with Ca2+ action potentials. The molecular and ionic mechanisms underlying these bursts of electrical activity remain unknown. We have observed that 10.2-12.8 mM Ca2+, 1 microM Bay K 8644 and 2 mM tetraethylammonium (TEA) trigger bursts of electrical activity and oscillations of intracellular free Ca2+ concentration ([Ca2+]i) in the presence of 100 microM tolbutamide. The [Ca2+]i was monitored from single islets of Langerhans using fura-2 microfluorescence techniques. Both the high-Ca(2+)- and Bay-K-8644-evoked [Ca2+]i oscillations overshot the [Ca2+]i recorded in tolbutamide. Nifedipine (10-20 microM) caused an immediate membrane hyperpolarization, which was followed by a slow depolarization to a level close to the burst active phase potential. The latter depolarization was accompanied by suppression of spiking activity. Exposure to high Ca2+ in the presence of nifedipine caused a steady depolarization of approximately 8 mV. Ionomycin (10 microM) caused membrane hyperpolarization in the presence of 7.7 mM Ca2+, which was not abolished by nifedipine. Charybdotoxin (CTX, 40-80 nM), TEA (2 mM) and quinine (200 microM) did not suppress the high-Ca(2+)-evoked bursts. It is concluded that: (1) the channel underlying the burst is sensitive to [Ca2+]i rises mediated by Ca2+ influx through L-type Ca2+ channels, (2) both the ATP-dependent K+ channel and the CTX- and TEA-sensitive Ca(2+)-dependent K+ channel are highly unlikely to provide the pacemaker current underlying the burst.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemoreception of phenolic acids and flavonoids in larvae of two species of Pieris

1. Chemosensory responses in lateral and medial maxillary sensilla styloconica to stimulation with phenolic acids and flavonoids were studied using electrophysiological methods in caterpillars of Pieris brassicae L. and Pieris rapae L. (Lepidoptera: Pieridae). 2. Of the 5 phenolic acids tested, those possessing ortho-substituted phenolic groups (chlorogenic and protocatechuic acids) were the most effective stimulants. 3. Of the 7 flavonoids examined, catechin was the most effective stimulant in the lateral sensillum of both species, while 3 others did not evoke a response at any of the concentrations tested. 4. Responses generally increased with increasing stimulus concentrations in the range tested (0.2–5.0 mm). P. rapae generally exhibited higher sensitivity thresholds. 5. Mixture experiments suggested that in the lateral sensillum of P. brassicae one cell and in the medial sensillum two cells were especially sensitive. 6. The anthocyanin cyanin chloride caused inhibition of spiking activity in several neurones. 7. Caterpillars reared on an artificial diet showed reduced sensitivity compared to caterpillars reared on a host plant. 8. Chemosensory activity was reflected in preference behaviour in dual choice situations. 9. Dose-response relations combined with phytochemical data permit the conclusion that naturally occurring levels of phenolic acids and flavonoids are stimulatory to some chemosensory neurones and can cause inhibition of activity in others.

Effect of cromakalim on smooth muscle cells of guinea-pig taenia caeci

Cromakalim caused hyperpolarization and reduction of the electrotonic potential in a concentration-dependent manner in smooth muscle cells of guinea-pig taenia caeci. There was a relatively constant change in the electrotonic potential under calcium-free, low-sodium and low-chloride conditions in the presence of cromakalim as compared to control conditions with Krebs solution. The effect of cromakalin (10 −5 M) was inhibited by glibenclamide (5 × 10 −5 M). These results indicate that cromakalim specifically promotes potassium efflux in smooth muscle cells of the guinea-pig taenia caeci via glibenclamide-sensitive potassium channels, to cause hyperpolarization, suppression of spike activity and relaxation.

Somatic and vagal afferent convergence on solitary tract neurons in cat: Electrophysiological characteristics

Electrophysiological characteristics are described for 67 neurones localized to subnuclei of the solitary tract or the area of the dorsal motor nucleus of the vagus in α-chloralose-anesthetized, paralysed cats which received vagal and hindlimb sural or peroneal nerve excitation. The peroneal and sural nerves were stimulated in an exposed hindlimb preparation; the ipsilateral vagus was stimulated at the cervical level. Compound action potentials were recorded from all three nerves. Neurons were recorded with extracellular microelectrodes from the brain stem solitary area contralateral to the stimulated somatic nerves. Ninety-one percent of the recorded neurons were spontaneously active. Eighteen percent and 5% of the neurons received only peroneal or sural excitation, respectively, while 59% of the neurons received convergent peroneal and sural excitation. Thirty-nine of the 67 neurons were also tested for vagal input of which 41 % responded with excitation. All of the neurons tested for vagal input also received converging excitation from one or both of the somatic nerves. Thirty-one percent of the vagal-excited neurons received converging input from both the peroneal and sural nerves. The combined mean minimal conduction velocity for peroneal and sural input was 31 ± 1 m/s (mean ± 1 S.E., range 9–54 m/s). Thirty-six percent of the peroneal and 31% of the sural afferents were Group II fibers. Significant periods of inhibition of spontaneous neuronal spike activity followed peroneal and sural excitation in 43 and 39% of the neurons, respectively. In many neurons, both excitation and inhibition of spike activity could be elicited at stimulus intensities as low as 1.2 times threshold for the lowest threshold fibers in each nerve. Somatic nerve-induced inhibition of spontaneous neuron activity without prior excitation was also observed. These results suggest that neurons of the solitary tract nuclei receive Group II and Group III somatic afferents which converge on neurons also receiving excitatory vagal input. Consequently, somesthetic and kinesthetic as well as visceral receptor activation may directly modulate solitary tract neurons. A possible conclusion is that the nucleus tractus solitarius is the initial central site of mediation of somatosympathetic reflexes. Modulation of the nucleus tractus solitarius by somatic afferents may then adjust sympathetic tone, via modulation of other medullary centers, in visceral and somatic tissues to match somatic metabolic needs.

The multiple action of bradykinin on smooth muscle of guinea-pig taenia caeci

The action of bradykinin on the smooth muscle of guinea-pig taenia caeci was studied by measuring changes in membrane potential, the contractile state of the muscle cells and intracellular calcium concentrations at 22°C in the presence of tetrodotoxin, yohimbine, prazosin, propranolol and atropine. The bradykinin response was characterised by an initial hyperpolarization and suppression of spike activity followed by a sustained depolarization and an increased spike activity accompanied by inhibition of the phasic contractions, an increase in muscle tone and the development of phasic contractions, respectively. The actions of bradykinin were not affected after B 1-bradykinin receptors were blocked with des-Arg 9-[Leu 8]bradykinin. The events induced by bradykinin were accompanied by an increase in the intracellular calcium concentration, as monitored by quin-2 fluorescence. The hyperpolarization and depolarization persisted in the presence of diltiazem (10 −5 M) and in calcium-free conditions. The hyperpolarization could be evoked only once in the absence of calcium and was inhibited in the presence of apamin and after stimulation of α 1-adrenoceptors or P 2-purinoceptors. Membrane conductance was decreased during the sustained depolarization. The membrane depolarization was abolished after the sodium concentration gradient was reduced. These results show a multiple action of bradykinin mediated via B 2-receptors: (1) on calcium mobilization associated with activation of potassium channels; (2) on calcium release from intracellular stores and (3) on receptor-activated sodium channels.

Aminergic modulation in lobster stomatogastric ganglion. I. Effects on motor pattern and activity of neurons within the pyloric circuit.

We investigated the effects of dopamine, octopamine, and serotonin on the motor output of the pyloric circuit in the stomatogastric ganglion of the lobster, Panulirus interruptus. Amines were bath applied at concentrations from 10(-8) to 10(-4) M, and the responses of the six classes of pyloric neurons were monitored both intracellularly and extracellularly. Each amine modified the pyloric motor pattern in a specific way. In addition, dopamine and octopamine were each able to produce different motor patterns at different concentrations. Amine effects on pyloric neurons included initiation and enhancement or inhibition of spike activity, changes in the phase relationships of neurons, and changes in the cycle frequency of the pyloric rhythm. These results show that the motor pattern produced by this well-studied central pattern generator circuit is highly plastic and can be modulated by endogenous biogenic amines.

Responses of limbic cortical neurons during instrumental conditioned reflexes in cats

Unit activity in cortical areas 24 and 32 was studied during conditioned placing reflex formation in cats. Neuronal responses in the limbic cortex of trained animals correlated with acoustic stimulation, the motor response, and also with the presentation of food reinforcement. In untrained animals 16% of neurons responded to acoustic stimulation. After training the number of neurons responding to sound in area 32 increased to 51.3%. Of the total number of neurons, 34.6% responded by initial excitation and 26.7% by inhibition of spike activity. The latent period of these responses was about 50 msec and their duration up to 200 msec. Similar but weaker responses were observed in area 24. Short-latency activation responses to conditioned and differential stimulation were similar in character. It is suggested that after training processes taking place in the limbic cortex may contribute to better perception of both conditioned and differential acoustic stimuli, irrespective of their functional significance.

Cutaneous mechanism of electroreceptor temperature sensitivity of the ampullae of Lorenzini

The potential difference on the receptor epithelium of the ampullae of Lorenzini and on the skin and also spike discharges of single electroreceptor nerve fibers in response to temperature stimulation of the region of the pores of the ampullae were studied in the Black Sea skateRaja clavata. Heating the skin in the region of the pore led to the appearance of a positive potential on the skin and on the epithelium of the ampulla, and to inhibition of spike activity. The time course of the change in potential reflected the course of change of temperature; the temperature coefficient was 100–150 µV/°C. Cooling the skin was accompanied by a negative deviation of potential on the skin and in the ampullary canal and by excitation of spike activity. During cooling the temperature coefficient was 30–50 µV/°C. It is concluded that spike activity of electroreceptors reflects changes in potential on the skin due to changes in temperature. The mechanism and biological significance of the phenomena discovered are discussed.

The action of apamin on guinea-pig taenia caeci

Apamin (10 −7 M), a substance extracted from bee venom ( apis mellifica) causes stimulation of the taenia caeci as seen from an increase in spike activity. The inhibitory effect of ATP or adrenaline (Adr) was reflected by hyperpolarization of the muscle cell, cessation of spike activity and relaxation of the muscle. The 42K efflux and the membrane conductance were enhanced in the presence of these substances. Apamine converted the hyperpolarization caused by ATP or Adr into a transient depolarization which produced contraction of the muscle cells. The changes in membrane conductance and 42K efflux were diminished by the bee toxin. Furthermore, the potassium-dependent phase of the action potential was lengthened by apamine. Reduction of the extracellular chloride or sodium concentration, blockade of the nervous system by TTX (3 × 10 −7 M) or inhibition of spike activity by D600 (3 × 10 −6 M) did not affect the excitatory and blocking action of apamin. A high concentration of the calcium antagonist D600 (10 −4 M) or omission of extracellular calcium was needed to reduce the transient depolarization evoked by ATP or Adr in the presence of apamin. It is concluded that apamin prevents the opening of the ATP- and Adr-sensitive and voltage-dependent potassium channels in guinea-pig taenia caeci.

Investigation of the mechanism of temperature sensitivity of the electroreceptors of ampullae of lorenzini

In experiments on Black Sea skates (Raja clavata), the potential of the receptor epithelium of the ampullae of Lorenzini and spike activity of single nerve fibers connected to them were investigated during electrical and temperature stimulation. Usually the potential within the canal was between 0 and −2 mV, and the input resistance of the ampulla 250–400 kΩ. Heating of the region of the receptor epithelium was accompanied by a negative wave of potential, an increase in input resistance, and inhibition of spike activity. With worsening of the animal's condition the transepithelial potential became positive (up to +10 mV) but the input resistance of the ampulla during stimulation with a positive current was nonlinear in some cases: a regenerative spike of positive polarity appeared in the channel. During heating, the spike response was sometimes reversed in sign. It is suggested that fluctuations of the transepithelial potential and spike responses to temperature stimulation reflect changes in the potential difference on the basal membrane of the receptor cells, which is described by a relationship of the Nernst's or Goldman's equation type.

Hair cell interactions in the statocyst of Hermissenda.

Hair cells in the statocyst of Hermissenda crassicornis respond to mechanical stimulation with a short latency (<2 ms) depolarizing generator potential that is followed by hyperpolarization and inhibition of spike activity. Mechanically evoked hyperpolarization and spike inhibition were abolished by cutting the static nerve, repetitive mechanical stimulation, tetrodotoxin (TTX), and Co(++). Since none of these procedures markedly altered the generator potential it was concluded that the hyperpolarization is an inhibitory synaptic potential and not a component of the mechanotransduction process. Intracellular recordings from pairs of hair cells in the same statocyst and in statocysts on opposite sides of the brain revealed that hair cells are connected by chemical and/or electrical synapses. All chemical interactions were inhibitory. Hyperpolarization and spike inhibition result from inhibitory interactions between hair cells in the same and in opposite statocysts.

Cortical coding of repetitive acoustic pulses

Recordings were obtained from 179 cells, 53 of which were studied intracellularly; among these 26 cells were studied extracellularly before being studied intracellularly. A subgroup of units was characterized by spike durations of about one-third normal. These are referred to as ‘thin-spike units’. The population of cells was classified in 4 categories on the basis of responses to trains of repetitive chicks: Lockers had discharges precisely time-locked to the individual clicks. This category could be further subdivided into regular-spike lockers and thin-spike lockers. Intracellular recordings of response to single clicks from regular-spike lockers showed a short EPSP followed by a long IPSP. The limiting rate of locking for each unit was defined to be the highest rate of click repetition at which clear locking of spike activity to individual clicks in the trains could be observed. At repetition rates higher than their limiting rate regular-spike lockers usually exhibited one or two spikes at the train onset and suppression of spike activity throughout the remainder of the train. Thin-spike lockers had high rates of ongoing (spontaneous) activity and for clicks presented at low repitition rates responded with time-locked spikes and spontaneous spike activity between the locked spikes. When the limiting rate was exceeded the thin-spike lockers showed a sustained but unsynchronized discharge for the duration of the click train. Intracellular records exhibited a predominance of driven EPSPs with very little inhibitory impingement. Thirty-nine percent of the experimental population were lockers. The distribution of limiting rates was broad, from 10/sec to 1000/sec, with the median between 50/sec and 100/sec. Some lockers were studied with repetitive noise bursts. Evoked patterns of spike activity and limiting rates of these units were quite similar for clicks and brief noise pulses. The lockers exhibit a temporal coding of the repetition rate of acoustic stimuli which when presented to human listeners are judged to have periodicity pitch. Groupers had spike responses loosely synchronized to low rates of repetitive clicks. Intracellular records showed that single clicks evoked long lasting IPSPs. Spike activity was suppressed following the click sometimes returning with a rate higher than the ongoing rate. The latency of the return of activity after suppression is quite variable. For click train stimulation at low repetition rates the spike occurrences were grouped in part of the period between individual clicks. This loose synchrony was lmited to click repetition rates below 50/sec. Sixteen percent of the cells studied (but no thin-spike units) were in the grouper category. Special responders had patterns of spike activity related to the stimulus but their spikes were not synchronized with the individual clicks. The response patterns to the whole train could be described by the usual terms, on, off, through, etc. Seventeen percent of the cells studied were in this category. Twenty-eight percent of the experimental population did not respond to repetitive click stimulation. Possible neural coding mechanisms for periodicity pitch and the relationship of the present categories to those suggested on the basis of tuning curves are discussed.

Properties of the epiphysis cerebri of the small-spotted dogfish shark, Scyliorhinus caniculus L.

A light stimulus, focused on the head of the dogfish shark ( Scyliorhinus caniculus) over the end vesicle of the epiphysis cerebri (pineal organ), elicits a positive slow wave accompanied by inhibition of spike activity which was recorded from the cut end of the epiphyseal stalk. A stimulus of4.3 × 10 −4lm/m 2 was sufficient to alter the on-going neural activity. From threshold to approximately 3 log units above threshold, there was good correlation between the amplitude of the slow potential and the inhibition of spikes. Further increases in the intensity of the stimulus did not elicit larger positive waves but greatly prolonged the duration of the inhibition of spikes. The observations can be best interpreted if the slow potentials arise from the ganglion cells and represent the summated inhibitory postsynaptic potentials transmitted electronically to the recording electrode. The spectral sensitivity of the epiphysis and the lateral eyes peak at 500 nm.

Time relations between the evoked potential and activity of hippocampal neurons

The time relations between the evoked potential (EP) and neuronal activity of the dorsal hippocampus in response to sciatic nerve stimulation were investigated in experiments conducted on rabbits paralyzed by tubocurarine. Two groups of neurons were distinguished on the basis of the type of their reaction to sciatic stimulation. Inhibition of background spike activity was found in the neurons of the first group (70.9%); in 37% of them inhibition was preceded by excitation in the form of a spike discharge or excitatory postsynaptic potential (EPSP) which coincided in time with the positive phase of the EP. During inhibition of spike activity the hyperpolarization potential was recorded intracellularly in a number of neurons, the latent period of which coincided with the latent period of the negative phase of the EP. Neurons of the second group (20%) were characterized by protracted excitation of spike activity, and the start of their excitation coincided with the start of the negative phase of the EP and hyperpolarization potential of the neurons of the first group. Different sensitivity of the two groups of neurons was noted. It is concluded that the EPSP of the pyramidal neurons of the hippocampus participates in generation of the positive phase of the EP, and the hyperpolarization potentials of these neurons participate in the generation of its negative phase. The possibility is not precluded that hippocampal neurons closer to the surface participate in the development of the negative phase of the EP.