Synaptic Origin of Early Sensory-evoked Oscillations in the Immature Thalamus.

During the critical period of postnatal development, brain maturation is extremely sensitive to external stimuli. Newborn rodents already have functional somatosensory pathways and the thalamus, but the cortex is still forming. Immature thalamic synapses may produce large postsynaptic potentials in immature neurons, while non-synaptic membrane currents remain relatively weak and slow. The thalamocortical system generates spontaneous and evoked early gamma and spindle-burst oscillations in newborn rodents. How relatively strong synapses and weak intrinsic currents interact with each other and how they contribute to early thalamic activities remains largely unknown. Here, we performed local field potential (LFP), juxtacellular, and patch-clamp recordings in the somatosensory thalamus of urethane-anesthetized rat pups at postnatal days 6-7 with one whisker stimulation. We removed the overlying cortex and hippocampus to reach the thalamus with electrodes. Deflection of only one (the principal) whisker induced spikes in a particular thalamic cell. Whisker deflection evoked a group of large-amplitude excitatory events, likely originating from lemniscal synapses and multiple inhibitory postsynaptic events in thalamocortical cells. Large-amplitude excitatory events produced a group of spike bursts and could evoke a depolarization block. Juxtacellular recordings confirmed the partial inactivation of spikes. Inhibitory events prevented inactivation of action potentials and gamma-modulated neuronal firing. We conclude that the interplay of strong excitatory and inhibitory synapses and relatively weak intrinsic currents produces sensory-evoked early gamma oscillations in thalamocortical cells. We also propose that sensory-evoked large-amplitude excitatory events contribute to evoked spindle-bursts.

Respiration organizes gamma synchrony in the prefronto-thalamic network.

Multiple cognitive operations are associated with the emergence of gamma oscillations in the medial prefrontal cortex (mPFC) although little is known about the mechanisms that control this rhythm. Using local field potential recordings from cats, we show that periodic bursts of gamma recur with 1 Hz regularity in the wake mPFC and are locked to the exhalation phase of the respiratory cycle. Respiration organizes long-range coherence in the gamma band between the mPFC and the nucleus reuniens the thalamus (Reu), linking the prefrontal cortex and the hippocampus. In vivo intracellular recordings of the mouse thalamus reveal that respiration timing is propagated by synaptic activity in Reu and likely underlies the emergence of gamma bursts in the prefrontal cortex. Our findings highlight breathing as an important substrate for long-range neuronal synchronization across the prefrontal circuit, a key network for cognitive operations.

Effects of Cortical Cooling on Activity Across Layers of the Rat Barrel Cortex.

Moderate cortical cooling is known to suppress slow oscillations and to evoke persistent cortical activity. However, the cooling-induced changes in electrical activity across cortical layers remain largely unknown. Here, we performed multi-channel local field potential (LFP) and multi-unit activity (MUA) recordings with linear silicone probes through the layers of single cortical barrel columns in urethane-anesthetized rats under normothermia (38°C) and during local cortical surface cooling (30°C). During cortically generated slow oscillations, moderate cortical cooling decreased delta wave amplitude, delta-wave occurrence, the duration of silent states, and delta wave-locked MUA synchronization. Moderate cortical cooling increased total time spent in the active state and decreased total time spent in the silent state. Cooling-evoked changes in the MUA firing rate in cortical layer 5 (L5) varied from increase to decrease across animals, and the polarity of changes in L5 MUA correlated with changes in total time spent in the active state. The decrease in temperature reduced MUA firing rates in all other cortical layers. Sensory-evoked MUA responses also decreased during cooling through all cortical layers. The cooling-dependent slowdown was detected at the fast time-scale with a decreased frequency of sensory-evoked high-frequency oscillations (HFO). Thus, moderate cortical cooling suppresses slow oscillations and desynchronizes neuronal activity through all cortical layers, and is associated with reduced firing across all cortical layers except L5, where cooling induces variable and non-consistent changes in neuronal firing, which are common features of the transition from slow-wave synchronization to desynchronized activity in the barrel cortex.

Moderate Cortical Cooling Eliminates Thalamocortical Silent States during Slow Oscillation.

Reduction in temperature depolarizes neurons by a partial closure of potassium channels but decreases the vesicle release probability within synapses. Compared with cooling, neuromodulators produce qualitatively similar effects on intrinsic neuronal properties and synapses in the cortex. We used this similarity of neuronal action in ketamine-xylazine-anesthetized mice and non-anesthetized mice to manipulate the thalamocortical activity. We recorded cortical electroencephalogram/local field potential (LFP) activity and intracellular activities from the somatosensory thalamus in control conditions, during cortical cooling and on rewarming. In the deeply anesthetized mice, moderate cortical cooling was characterized by reversible disruption of the thalamocortical slow-wave pattern rhythmicity and the appearance of fast LFP spikes, with frequencies ranging from 6 to 9 Hz. These LFP spikes were correlated with the rhythmic IPSP activities recorded within the thalamic ventral posterior medial neurons and with depolarizing events in the posterior nucleus neurons. Similar cooling of the cortex during light anesthesia rapidly and reversibly eliminated thalamocortical silent states and evoked thalamocortical persistent activity; conversely, mild heating increased thalamocortical slow-wave rhythmicity. In the non-anesthetized head-restrained mice, cooling also prevented the generation of thalamocortical silent states. We conclude that moderate cortical cooling might be used to manipulate slow-wave network activity and induce neuromodulator-independent transition to activated states. Significance statement: In this study, we demonstrate that moderate local cortical cooling of lightly anesthetized or naturally sleeping mice disrupts thalamocortical slow oscillation and induces the activated local field potential pattern. Mild heating has the opposite effect; it increases the rhythmicity of thalamocortical slow oscillation. Our results demonstrate that slow oscillation can be influenced by manipulations to the properties of cortical neurons without changes in neuromodulation.

Global intracellular slow-wave dynamics of the thalamocortical system.

It is widely accepted that corticothalamic neurons recruit the thalamus in slow oscillation, but global slow-wave thalamocortical dynamics have never been experimentally shown. We analyzed intracellular activities of neurons either from different cortical areas or from a variety of specific and nonspecific thalamic nuclei in relation to the phase of global EEG signal in ketamine-xylazine anesthetized mice. We found that, on average, slow-wave active states started off within frontal cortical areas as well as higher-order and intralaminar thalamus (posterior and parafascicular nuclei) simultaneously. Then, the leading edge of active states propagated in the anteroposterior/lateral direction over the cortex at ∼40 mm/s. The latest structure we recorded within the slow-wave cycle was the anterior thalamus, which followed active states of the retrosplenial cortex. Active states from different cortical areas tended to terminate simultaneously. Sensory thalamic ventral posterior medial and lateral geniculate nuclei followed cortical active states with major inhibitory and weak tonic-like "modulator" EPSPs. In these nuclei, sharp-rising, large-amplitude EPSPs ("drivers") were not modulated by cortical slow waves, suggesting their origin in ascending pathways. The thalamic active states in other investigated nuclei were composed of depolarization: some revealing "driver"- and "modulator"-like EPSPs, others showing "modulator"-like EPSPs only. We conclude that sensory thalamic nuclei follow the propagating cortical waves, whereas neurons from higher-order thalamic nuclei display "hub dynamics" and thus may contribute to the generation of cortical slow waves.

Spontaneous bursting activity in the developing entorhinal cortex.

Periodic spontaneous activity represents an important attribute of the developing nervous system. The entorhinal cortex (EC) is a crucial component of the medial temporal lobe memory system. Yet, little is known about spontaneous activity in the immature EC. Here, we investigated spontaneous field potential (fp) activity and intrinsic firing patterns of medial EC layer III principal neurons in brain slices obtained from rats at the first two postnatal weeks. A fraction of immature layer III neurons spontaneously generated prolonged (2-20 s) voltage-dependent intrinsic bursting activity. Prolonged bursts were dependent on the extracellular concentration of Ca(2+) ([Ca(2+)](o)). Thus, reduction of [Ca(2+)](o) increased the fraction of neurons with prolonged bursting by inducing intrinsic bursts in regularly firing neurons. In 1 mm [Ca(2+)](o), the percentages of neurons showing prolonged bursts were 53%, 81%, and 29% at postnatal day 5 (P5)-P7, P8-P10, and P11-P13, respectively. Prolonged intrinsic bursting activity was blocked by buffering intracellular Ca(2+) with BAPTA, and by Cd(2+), flufenamic acid (FFA), or TTX, and was suppressed by nifedipine and riluzole, suggesting that the Ca(2+)-sensitive nonspecific cationic current (I(CAN)) and the persistent Na(+) current (I(Nap)) underlie this effect. Indeed, a 0.2-1 s suprathreshold current step stimulus elicited a terminated plateau potential in these neurons. fp recordings at P5-P7 showed periodic spontaneous glutamate receptor-mediated events (sharp fp events or prolonged fp bursts) which were blocked by FFA. Slow-wave network oscillations become a dominant pattern at P11-P13. We conclude that prolonged intrinsic bursting activity is a characteristic feature of developing medial EC layer III neurons that might be involved in neuronal and network maturation.