Rate maintenance and resonance in the entorhinal cortex

Throughout the brain, neurons encode information in fundamental units of spikes. Each spike represents the combined thresholding of synaptic inputs and intrinsic neuronal dynamics. Here, we address a basic question of spike train formation: how do perithreshold synaptic inputs perturb the output of a spiking neuron? We recorded from single entorhinal principal cells in vitro and drove them to spike steadily at ～5 Hz (theta range) with direct current injection, then used a dynamic‐clamp to superimpose strong excitatory conductance inputs at varying rates. Neurons spiked most reliably when the input rate matched the intrinsic neuronal firing rate. We also found a striking tendency of neurons to preserve their rates and coefficients of variation, independently of input rates. As mechanisms for this rate maintenance, we show that the efficacy of the conductance inputs varied with the relationship of input rate to neuronal firing rate, and with the arrival time of the input within the natural period. Using a novel method of spike classification, we developed a minimal Markov model that reproduced the measured statistics of the output spike trains and thus allowed us to identify and compare contributions to the rate maintenance and resonance. We suggest that the strength of rate maintenance may be used as a new categorization scheme for neuronal response and note that individual intrinsic spiking mechanisms may play a significant role in forming the rhythmic spike trains of activated neurons; in the entorhinal cortex, individual pacemakers may dominate production of the regional theta rhythm.     

Gain Modulation of Cholinergic Neurons in the Medial Septum‐Diagonal Band of Broca Through Hyperpolarization

Hippocampal network oscillations are important for learning and memory. Theta rhythms are involved in attention, navigation, and memory encoding, whereas sharp wave‐ripple complexes are involved in memory consolidation. Cholinergic neurons in the medial septum‐diagonal band of Broca (MS‐DB) influence both types of hippocampal oscillations, promoting theta rhythms and suppressing sharp wave‐ripples. They also receive frequency‐dependent hyperpolarizing feedback from hippocamposeptal connections, potentially affecting their role as neuromodulators in the septohippocampal circuit. However, little is known about how the integration properties of cholinergic MS‐DB neurons change with hyperpolarization. By potentially altering firing behavior in cholinergic neurons, hyperpolarizing feedback from the hippocampal neurons may, in turn, change hippocampal network activity. To study changes in membrane integration properties in cholinergic neurons in response to hyperpolarizing inputs, we used whole‐cell patch‐clamp recordings targeting genetically labeled, choline acetyltransferase‐positive neurons in mouse brain slices. Hyperpolarization of cholinergic MS‐DB neurons resulted in a long‐lasting decrease in spike firing rate and input‐output gain. Additionally, voltage‐clamp measures implicated a slowly inactivating, 4‐AP‐insensitive, outward K⁺ conductance. Using a conductance‐based model of cholinergic MS‐DB neurons, we show that the ability of this conductance to modulate firing rate and gain depends on the expression of an experimentally verified shallow intrinsic spike frequency‐voltage relationship. Together, these findings point to a means through which negative feedback from hippocampal neurons can influence the role of cholinergic MS‐DB neurons. © 2016 Wiley Periodicals, Inc.     

Frequency‐dependent regulation of intrinsic excitability by voltage‐activated membrane conductances,computational modeling and dynamic clamp

As one of the most unique properties of nerve cells, their intrinsic excitability allows them to transform synaptic inputs into action potentials. This process reflects a complex interplay between the synaptic inputs and the voltage‐dependent membrane currents of the postsynaptic neuron. While neurons in natural conditions mostly fire under the action of intense synaptic bombardment and receive fluctuating patterns of excitation and inhibition, conventional techniques to characterize intrinsic excitability mainly utilize static means of stimulation. Recently, we have shown that voltage‐gated membrane currents regulate the firing responses under current step stimulation and under physiologically more realistic inputs in a differential manner. At the same time, a multitude of neuron types have been shown to exhibit some form of subthreshold resonance that potentially allows them to respond to synaptic inputs in a frequency‐selective manner. In this study, we performed virtual experiments in computational models of neurons to examine how specific voltage‐gated currents regulate their excitability under simulated frequency‐modulated synaptic inputs. The model simulations and subsequent dynamic clamp experiments on mouse hippocampal pyramidal neurons revealed that the impact of voltage‐gated currents in regulating the firing output is strongly frequency‐dependent and mostly affecting the synaptic integration at theta frequencies. Notably, robust frequency‐dependent regulation of intrinsic excitability was observed even when conventional analysis of membrane impedance suggested no such tendency. Consequently, plastic or homeostatic regulation of intrinsic membrane properties can tune the frequency selectivity of neuron populations in a way that is not readily expected from subthreshold impedance measurements.     

Fast‐spiking interneurons of the rat ventral striatum: temporal coordination of activity with principal cells and responsiveness to reward

Although previous in vitro studies revealed inhibitory synaptic connections of fast‐spiking interneurons to principal cells in the striatum, uncertainty remains about the nature of the behavioural events that correlate with changes in interneuron activity and about the temporal coordination of interneuron firing with spiking of principal cells under natural conditions. Using in vivo tetrode recordings from the ventral striatum in freely moving rats, fast‐spiking neurons were distinguished from putative medium‐sized spiny neurons on the basis of their spike waveforms and rates. Cross‐correlograms of fast‐spiking and putative medium‐sized spiny neuron firing patterns revealed a variety of temporal relationships, including peaks of concurrent firing and transient decrements in medium‐sized spiny neuron spiking around fast‐spiking unit activity. Notably, the onset of these decrements was mostly in advance of the fast‐spiking unit firing. Many of these temporal relationships were dependent on the sleep–wake state. Coordinated activity was also found amongst pairs of the same phenotype, both fast‐spiking units and putative medium‐sized spiny neurons, which was often marked by a broad peak of concurrent firing. When studying fast‐spiking neurons in a reward‐searching task, they generally showed a pre‐reward ramping increment in firing rate but a decrement specifically when the rat received reward. In conclusion, our data indicate that various forms of temporally coordinated activity exist amongst ventral striatal interneurons and principal cells, which cannot be explained by feed‐forward inhibitory circuits alone. Furthermore, firing patterns of ventral striatal fast‐spiking interneurons do not merely correlate with the general arousal state of the animal but display distinct reward‐related changes in firing rate.     

Intrinsic subthreshold oscillations extend the influence of inhibitory synaptic inputs on cortical pyramidal neurons

Fast inhibitory synaptic inputs, which cause conductance changes that typically last for 10–100 ms, participate in the generation and maintenance of cortical rhythms. We show here that these fast events can have influences that outlast the duration of the synaptic potentials by interacting with subthreshold membrane potential oscillations. Inhibitory postsynaptic potentials (IPSPs) in cortical neurons in vitro shifted the oscillatory phase for several seconds. The phase shift caused by two IPSPs or two current pulses summed non‐linearly. Cholinergic neuromodulation increased the power of the oscillations and decreased the magnitude of the phase shifts. These results show that the intrinsic conductances of cortical pyramidal neurons can carry information about inhibitory inputs and can extend the integration window for synaptic input.     

Interactions between behaviorally relevant rhythms and synaptic plasticity alter coding in the piriform cortex

Understanding how neural and behavioral timescales interact to influence cortical activity and stimulus coding is an important issue in sensory neuroscience. In air-breathing animals, voluntary changes in respiratory frequency alter the temporal patterning olfactory input. In the olfactory bulb, these behavioral timescales are reflected in the temporal properties of mitral/tufted (M/T) cell spike trains. As the odor information contained in these spike trains is relayed from the bulb to the cortex, interactions between presynaptic spike timing and short-term synaptic plasticity dictate how stimulus features are represented in cortical spike trains. Here, we demonstrate how the timescales associated with respiratory frequency, spike timing, and short-term synaptic plasticity interact to shape cortical responses. Specifically, we quantified the timescales of short-term synaptic facilitation and depression at excitatory synapses between bulbar M/T cells and cortical neurons in slices of mouse olfactory cortex. We then used these results to generate simulated M/T population synaptic currents that were injected into real cortical neurons. M/T population inputs were modulated at frequencies consistent with passive respiration or active sniffing. We show how the differential recruitment of short-term plasticity at breathing versus sniffing frequencies alters cortical spike responses. For inputs at sniffing frequencies, cortical neurons linearly encoded increases in presynaptic firing rates with increased phase-locked, firing rates. In contrast, at passive breathing frequencies, cortical responses saturated with changes in presynaptic rate. Our results suggest that changes in respiratory behavior can gate the transfer of stimulus information between the olfactory bulb and cortex.     

Stimulus-selective spiking is driven by the relative timing of synchronous excitation and disinhibition in cat striate neurons in vivo

What patterns of synaptic input cause cortical neurons to fire action potentials? Are they stochastic in nature, or do action potentials arise from the specific timing of synaptic input? We addressed these questions by measuring the membrane potential fluctuations associated with the generation of visually evoked action potentials in cat striate cortical neurons in vivo. In response to visual stimulation, action potentials occurred at the crest of large‐amplitude, transient depolarizations (TDs) riding on sustained depolarization of the membrane potential. The magnitude, duration and rate of depolarization of these transient events were tuned for stimulus orientation. Using numerical simulations, we find that these transient events can arise from the temporal interplay between synchronous excitation and inhibition. To validate these findings, we made conductance measurements, at the preferred stimulus orientation, and showed that the TDs arise either from an increase in excitatory conductance, or from a combination of increased excitatory and decreased inhibitory conductance, both riding on sustained changes in synaptic conductances. The properties of the TDs and their underlying conductance suggest that they arise from a specific temporal interplay between synchronous excitatory and inhibitory synaptic inputs. Our results illustrate a mechanism by which the timing of synaptic inputs determines much of the spiking activity in striate cortical neurons.     

Inhibitory short‐term plasticity modulates neuronal activity in the rat entopeduncular nucleus in vitro

The entopeduncular nucleus (EP) is one of the basal ganglia output nuclei integrating synaptic information from several pathways within the basal ganglia. The firing of EP neurons is modulated by two streams of inhibitory synaptic transmission, the direct pathway from the striatum and the indirect pathway from the globus pallidus. These two inhibitory pathways continuously modulate the firing of EP neurons. However, the link between these synaptic inputs to neuronal firing in the EP is unclear. To investigate this input–output transformation we performed whole‐cell and perforated‐patch recordings from single neurons in the entopeduncular nucleus in rat brain slices during repetitive stimulation of the striatum and the globus pallidus at frequencies within the in vivo activity range of these neurons. These recordings, supplemented by compartmental modelling, showed that GABAergic synapses from the striatum, converging on EP dendrites, display short‐term facilitation and that somatic or proximal GABAergic synapses from the globus pallidus show short‐term depression. Activation of striatal synapses during low presynaptic activity decreased postsynaptic firing rate by continuously increasing the inter‐spike interval. Conversely, activation of pallidal synapses significantly affected postsynaptic firing during high presynaptic activity. Our data thus suggest that low‐frequency striatal output may be encoded as progressive phase shifts in downstream nuclei of the basal ganglia while high‐frequency pallidal output may continuously modulate EP firing.     

The small‐conductance calcium‐activated potassium channel is a key modulator of firing and long‐term depression in the dorsal striatum

The striatum is considered to be critical for the control of goal‐directed action, with the lateral dorsal striatum (latDS) being implicated in modulation of habits and the nucleus accumbens thought to represent a limbic–motor interface. Although medium spiny neurons from different striatal subregions exhibit many similar properties, differential firing and synaptic plasticity could contribute to the varied behavioral roles across subregions. Here, we examined the contribution of small‐conductance calcium‐activated potassium channels (SKs) to action potential generation and synaptic plasticity in adult rat latDS and nucleus accumbens shell (NAS) projection neurons in vitro. The SK‐selective antagonist apamin exerted a prominent effect on latDS firing, significantly decreasing the interspike interval. Furthermore, prolonged latDS depolarization increased the interspike interval and reduced firing, and this enhancement was reversed by apamin. In contrast, NAS neurons exhibited greater basal firing rates and less regulation of firing by SK inhibition and prolonged depolarization. LatDS neurons also had greater SK currents than NAS neurons under voltage‐clamp. Importantly, SK inhibition with apamin facilitated long‐term depression (LTD) induction in the latDS but not the NAS, without alterations in glutamate release. In addition, SK activation in the latDS prevented LTD induction. Greater SK function in the latDS than in the NAS was not secondary to differences in sodium or inwardly rectifying potassium channel function, and apamin enhancement of firing did not reflect indirect action through cholinergic interneurons. Thus, these data demonstrate that SKs are potent modulators of action potential generation and LTD in the dorsal striatum, and could represent a fundamental cellular mechanism through which habits are regulated.     

Functional characterization of ether‐à‐go‐go‐related gene potassium channels in midbrain dopamine neurons – implications for a role in depolarization block

Bursting activity by midbrain dopamine neurons reflects the complex interplay between their intrinsic pacemaker activity and synaptic inputs. Although the precise mechanism responsible for the generation and modulation of bursting in vivo has yet to be established, several ion channels have been implicated in the process. Previous studies with nonselective blockers suggested that ether‐à‐go‐go‐related gene (ERG) K⁺ channels are functionally significant. Here, electrophysiology with selective chemical and peptide ERG channel blockers (E‐4031 and rBeKm‐1) and computational methods were used to define the contribution made by ERG channels to the firing properties of midbrain dopamine neurons in vivo and in vitro. Selective ERG channel blockade increased the frequency of spontaneous activity as well as the response to depolarizing current pulses without altering spike frequency adaptation. ERG channel block also accelerated entry into depolarization inactivation during bursts elicited by virtual NMDA receptors generated with the dynamic clamp, and significantly prolonged the duration of the sustained depolarization inactivation that followed pharmacologically evoked bursts. In vivo, somatic ERG blockade was associated with an increase in bursting activity attributed to a reduction in doublet firing. Taken together, these results show that dopamine neuron ERG K⁺ channels play a prominent role in limiting excitability and in minimizing depolarization inactivation. As the therapeutic actions of antipsychotic drugs are associated with depolarization inactivation of dopamine neurons and blockade of cardiac ERG channels is a prominent side effect of these drugs, ERG channels in the central nervous system may represent a novel target for antipsychotic drug development.     

Stimulus intensity determines experience‐dependent modifications in neocortical neuron firing rates

Although subthreshold inputs of neocortical sensory neurons are broadly tuned, the spiking output is more restricted. These subthreshold inputs provide a substrate for stimulus intensity‐dependent changes their spiking output, as well as for experience‐dependent plasticity to alter firing properties. Here we investigated how different stimulus intensities modified the firing output of individual neurons in layer 2/3 of the mouse barrel cortex. Decreasing stimulus intensity over a 30‐fold range lowered the firing rates evoked by principal whisker stimulation and reduced the overall size of the responding ensemble in whisker‐undeprived animals. We then examined how these responses were changed after single‐whisker experience (SWE). After 7 days of SWE, the mean magnitude of response to spared whisker stimulation at the highest stimulus intensity was not altered. However, lower‐intensity whisker stimulation revealed a more than 10‐fold increase in mean firing output compared with control animals. Also, under control conditions, only ~15% of neurons showed any firing at low stimulus intensity, compared with more than 70% of neurons after SWE. However, response changes measured in the immediately surrounding representations were detected only for the highest stimulus intensity. Overall, these data showed that the measurement of experience‐dependent changes in the spike output of neocortical neurons was highly dependent upon stimulus intensity.     

Bidirectional plasticity of intrinsic excitability controls sensory inputs efficiency in layer 5 barrel cortex neurons in vivo

Responsiveness of cortical neurons to sensory inputs can be altered by experience and learning. While synaptic plasticity is generally proposed as the underlying cellular mechanism, possible contributions of activity-dependent changes in intrinsic excitability remain poorly investigated. Here, we show that periods of rhythmic firing in rat barrel cortex layer 5 pyramidal neurons can trigger a long-lasting increase or decrease in their membrane excitability in vivo. Potentiation of cortical excitability consisted of an increased firing in response to intracellular stimulation and a reduction in threshold current for spike initiation. Conversely, depression of cortical excitability was evidenced by an augmented firing threshold leading to a reduced current-evoked spiking. The direction of plasticity depended on the baseline level of spontaneous firing rate and cell excitability. We also found that changes in intrinsic excitability were accompanied by corresponding modifications in the effectiveness of sensory inputs. Potentiation and depression of cortical neuron excitability resulted, respectively, in an increased or decreased firing probability on whisker-evoked synaptic responses, without modifications in the synaptic strength itself. These data suggest that bidirectional intrinsic plasticity could play an important role in experience-dependent refinement of sensory cortical networks.     

Balanced synaptic currents underlie low‐frequency oscillations in the subiculum

Numerous synaptic and intrinsic membrane mechanisms have been proposed for generating oscillatory activity in the hippocampus. Few studies, however, have directly measured synaptic conductances and membrane properties during oscillations. The time course and relative contribution of excitatory and inhibitory synaptic conductances, as well as the role of intrinsic membrane properties in amplifying synaptic inputs, remains unclear. To address this issue, we used an isolated whole hippocampal preparation that generates autonomous low‐frequency oscillations near the theta range. Using 2‐photon microscopy and expression of genetically encoded fluorophores, we obtained on‐cell and whole‐cell patch recordings of pyramidal cells and fast‐firing interneurons in the distal subiculum. Pyramidal cell and interneuron spiking shared similar phase‐locking to local field potential oscillations. In pyramidal cells, spiking resulted from a concomitant and balanced increase in excitatory and inhibitory synaptic currents. In contrast, interneuron spiking was driven almost exclusively by excitatory synaptic current. Thus, similar to tightly balanced networks underlying hippocampal gamma oscillations and ripples, balanced synaptic inputs in the whole hippocampal preparation drive highly phase‐locked spiking at the peak of slower network oscillations.     

The vestibulo‐ and preposito‐cerebellar cholinergic neurons of a ChAT‐tdTomato transgenic rat exhibit heterogeneous firing properties and the expression of various neurotransmitter receptors

Cerebellar function is regulated by cholinergic mossy fiber inputs that are primarily derived from the medial vestibular nucleus (MVN) and prepositus hypoglossi nucleus (PHN). In contrast to the growing evidence surrounding cholinergic transmission and its functional significance in the cerebellum, the intrinsic and synaptic properties of cholinergic projection neurons (ChPNs) have not been clarified. In this study, we generated choline acetyltransferase (ChAT)‐tdTomato transgenic rats, which specifically express the fluorescent protein tdTomato in cholinergic neurons, and used them to investigate the response properties of ChPNs identified via retrograde labeling using whole‐cell recordings in brainstem slices. In response to current pulses, ChPNs exhibited two afterhyperpolarisation (AHP) profiles and three firing patterns; the predominant AHP and firing properties differed between the MVN and PHN. Morphologically, the ChPNs were separated into two types based on their soma size and dendritic extensions. Analyses of the firing responses to time‐varying sinusoidal current stimuli revealed that ChPNs exhibited different firing modes depending on the input frequencies. The maximum frequencies in which each firing mode was observed were different between the neurons that exhibited distinct firing patterns. Analyses of the current responses to the application of neurotransmitter receptor agonists revealed that the ChPNs expressed (i) AMPA‐ and NMDA‐type glutamate receptors, (ii) GABA_A and glycine receptors, and (iii) muscarinic and nicotinic acetylcholine receptors. The current responses mediated by these receptors of MVN ChPNs were not different from those of PHN ChPNs. These findings suggest that ChPNs receive various synaptic inputs and encode those inputs appropriately across different frequencies.     

3‐Hz subthreshold oscillations of CA2 neurons In vivo

The CA2 region is unique in the hippocampus; it receives direct synaptic innervations from several hypothalamic nuclei and expresses various receptors of neuromodulators, including adenosine, vasopressin, and oxytocin. Furthermore, the CA2 region may have distinct brain functions, such as the control of instinctive and social behaviors; however, little is known about the dynamics of the subthreshold membrane potentials of CA2 neurons in vivo. We conducted whole‐cell current‐clamp recordings from CA2 pyramidal cells in urethane‐anesthetized mice and monitored the intrinsic fluctuations in their membrane potentials. The CA2 pyramidal cells emitted spontaneous action potentials at mean firing rates of ～0.8 Hz. In approximately half of the neurons, the subthreshold membrane potential oscillated at ～3 Hz. In two neurons, we obtained simultaneous recordings of local field potentials from the CA1 stratum radiatum and demonstrated that the 3‐Hz oscillations of CA2 neurons were not correlated with CA1 field potentials. In tetrodotoxin‐perfused acute hippocampal slices, the membrane potentials of CA2 pyramidal cells were not preferentially entrained to 3‐Hz sinusoidal current inputs, which suggest that intracellular 3‐Hz oscillations reflect the neuronal dynamics of the surrounding networks. © 2016 Wiley Periodicals, Inc.     

Subthreshold delta‐frequency resonance in thalamic reticular neurons

The thalamic reticular nucleus (nRt) is an assembly of GABAergic projection neurons that participate in the generation of brain rhythms during synchronous sleep and absence epilepsy. NRt cells receive inhibitory and excitatory synaptic inputs, and are endowed with an intricate set of intrinsic conductances. However, little is known about how intrinsic and synaptic properties interact to generate rhythmic discharges in these neurons. In order to better understand this interaction, I studied the subthreshold responses of nRt cells to time‐varying inputs. Patch‐clamp recordings were performed in acute slices of rat thalamus (postnatal days 12–21). Sinusoidal current waveforms of linearly changing frequencies were injected into the soma, and the resulting voltage oscillations were recorded. At the resting membrane potential, the impedance profile showed a characteristic resonance at 1.7 Hz. The relative strength of the resonance was 1.2, and increased with membrane hyperpolarization. Small suprathreshold current injections led to preferred spike generation at the resonance frequency. Bath application of ZD7288 or Cs⁺, inhibitors of the hyperpolarization‐activated cation current (I_h), transformed the resonance into low‐pass behaviour, whereas the T‐channel blockers mibefradil and Ni²⁺ decreased the strength of the resonance. It is concluded that nRt cells have an I_h‐mediated intrinsic frequency preference in the subthreshold voltage range that favours action potential generation in the delta‐frequency band.     

Striatal GABAergic interneuron dysfunction in the Q175 mouse model of Huntington's disease

The pathological hallmark of Huntington's disease (HD) is the massive loss of striatal and cortical neurons. Until recently, it was believed that striatal interneurons were spared from degeneration. This view has changed after the demonstration that parvalbumin (PV)‐expressing interneurons also are vulnerable in humans. Here we compared morphological and functional changes of striatal fast‐spiking interneurons (FSIs) and low‐threshold spiking (LTS) interneurons in the Q175 mouse model of HD at presymptomatic (2 months) and symptomatic (12 months) stages of the disease. Electrophysiological intrinsic and synaptic properties of FSIs were significantly altered in symptomatic mice compared to wild‐type (WT) littermates. Overall, FSIs became more excitable with disease progression. Sholl analysis also revealed a significant loss of dendritic complexity and excitatory synaptic inputs. The basic membrane and synaptic properties of LTS interneurons were similar in Q175 and WT mice regardless of disease stage. The resilience of LTS interneurons could be related to their sparsity of excitatory synaptic inputs compared with FSIs. However, in symptomatic mice, a subpopulation of LTS interneurons displayed an increase in action potential firing within oscillating bursts. Thus, we conclude that while both FSI and LTS interneurons demonstrate increases in excitability, the HD mutation differentially affects their membrane and synaptic properties as well as their ability to respond to compensatory challenges presented during the late stage of the disease. Alterations in GABAergic interneuron intrinsic activity and responsiveness to incoming signals may significantly affect SPN output thus contributing to abnormal motor movements in patients afflicted with HD.     

SK channels modulate the excitability and firing precision of projection neurons in the robust nucleus of the arcopallium in adult male zebra finches

Objective Motor control is encoded by neuronal activity. Small conductance Ca2+-activated K+ channels (SK channels) maintain the regularity and precision of firing by contributing to the afterhyperpolarization (AHP) of the action potential in mammals. However, it is not clear how SK channels regulate the output of the vocal motor system in songbirds. The premotor robust nucleus of the arcopallium (RA) in the zebra finch is responsible for the output of song information. The temporal pattern of spike bursts in RA projection neurons is associated with the timing of the acoustic features of birdsong. Methods The firing properties of RA projection neurons were analyzed using patch clamp whole-cell and cell-attached recording techniques. Results SK channel blockade by apamin decreased the AHP amplitude and increased the evoked firing rate in RA projection neurons. It also caused reductions in the regularity and precision of firing. RA projection neurons displayed regular spontaneous action potentials, while apamin caused irregular spontaneous firing but had no effect on the firing rate. In the absence of synaptic inputs, RA projection neurons still had spontaneous firing, and apamin had an evident effect on the firing rate, but caused no significant change in the firing regularity, compared with apamin application in the presence of synaptic inputs. Conclusion SK channels contribute to the maintenance of firing regularity in RA projection neurons which requires synaptic activity, and consequently ensures the precision of song encoding.     

Time‐varying synchronous cell ensembles during consummatory periods correlate with variable numbers of place cell spikes

Spike rates of a hippocampal place cell are not constant and vary even when an animal visits an identical place field with nearly identical behavior. As one potential neurophysiological source underlying place cell spiking variability, we focused on the temporally fluctuating activity states of neuronal ensembles. Spike patterns of hippocampal neurons were recorded from rats performing a linear track task. Within a single consummatory period, similar sets of neurons were more frequently recruited in synchronous firing events, whereas different synchronized firing patterns of neuronal populations tended to be identified in different consummatory periods. A linear regression analysis indicated that the time‐varying activation patterns of neuronal populations during consummatory periods are correlated with the spike rates of a place cell within its place field during running. These findings suggest that place cell in‐field spiking is not only triggered by static inputs that represent external environments but also strongly depends on the time‐varying internal states of neuronal populations.     

Generation of resonance‐dependent oscillation by mGluR‐I activation switches single spiking to bursting in mesencephalic trigeminal sensory neurons

The primary sensory neurons supplying muscle spindles of jaw‐closing muscles are unique in that they have their somata in the mesencephalic trigeminal nucleus (MTN) in the brainstem, thereby receiving various synaptic inputs. MTN neurons display bursting upon activation of glutamatergic synaptic inputs while they faithfully relay respective impulses arising from peripheral sensory organs. The persistent sodium current (I_NaP) is reported to be responsible for both the generation of bursts and the relay of impulses. We addressed how I_NaP is controlled either to trigger bursts or to relay respective impulses as single spikes in MTN neurons. Protein kinase C (PKC) activation enhanced I_NaP only at low voltages. Spike generation was facilitated by PKC activation at membrane potentials more depolarized than the resting potential. By injection of a ramp current pulse, a burst of spikes was triggered from a depolarized membrane potential whereas its instantaneous spike frequency remained almost constant despite the ramp increases in the current intensity beyond the threshold. A puff application of glutamate preceding the ramp pulse lowered the threshold for evoking bursts by ramp pulses while chelerythrine abolished such effects of glutamate. Dihydroxyphenylglycine, an agonist of mGluR1/5, also caused similar effects, and increased both the frequency and impedance of membrane resonance. Immunohistochemistry revealed that glutamatergic synapses are made onto the stem axons, and that mGluR1/5 and Nav1.6 are co‐localized in the stem axon. Taken together, glutamatergic synaptic inputs onto the stem axon may be able to switch the relaying to the bursting mode.