Scientific Understanding of Consciousness
Thalamocortical System Development
Science 14 October 2011: Vol. 334 no. 6053 pp. 226-229
Early Gamma Oscillations Synchronize Developing Thalamus and Cortex
Marat Minlebaev1,2, Matthew Colonnese1,2, Timur Tsintsadze1,2, Anton Sirota3, Roustem Khazipov1,2
1INSERM U901, 163 Avenue de Luminy, B.P. 13, 13273 Marseille, France.
2Université Aix-Marseille, 163 Avenue de Luminy, 13273 Marseille, France.
3University of Tuebingen Center for Integrative Neuroscience, Paul-Ehrlich Strasse 15, Tuebingen 76072, Germany.
During development, formation of topographic maps in sensory cortex requires precise temporal binding in thalamocortical networks. However, the physiological substrate for such synchronization is unknown. We report that early gamma oscillations (EGOs) enable precise spatiotemporal thalamocortical synchronization in the neonatal rat whisker sensory system. Driven by a thalamic gamma oscillator and initially independent of cortical inhibition, EGOs synchronize neurons in a single thalamic barreloid and corresponding cortical barrel and support plasticity at developing thalamocortical synapses. We propose that the multiple replay of sensory input in thalamocortical circuits during EGOs allows thalamic and cortical neurons to be organized into vertical topographic functional units before the development of horizontal binding in adult brain.
Sensory Cortex Organized As a Topographic Map
Sensory cortex is organized as a topographic map consisting of arrays of columns that each receive an input from a particular region of sensory space. In the rodent “barrel” cortex, each cortical barrel column receives a specific input, conveyed via the thalamus, from a corresponding whisker. Development of the topographic thalamocortical connections depends critically on activity driven by the whiskers. During development, sensory input triggers various cortical activity patterns. However, it remains unknown how the sensory input from a single whisker is processed in the corresponding developing cortical column.
We found that in postnatal days 2 to 7 (P2 to P7), rats brief single principal whisker (PW) deflections evoke an oscillatory local field potential (LFP) response in the gamma band in the corresponding cortical barrel (peak frequency 55 ±2 Hz; n = 45 rats). Multiunit activity (MUA), gamma oscillation power, and the current sinks of these early gamma oscillations (EGOs) were maximal in the granular (Gr) layer. EGOs were time-locked to the stimulus and were apparent in the stimulus-triggered average LFP and MUA time histograms. Gr MUA was strongly phase-modulated by EGOs and occurred during the descending phase and troughs of gamma cycles (figs. S1 and S2C). Day-by-day analysis revealed that power in the gamma band increased from birth to attain maximal values at P2 to P7 and abruptly declined at P8, followed by a gradual increase both in spontaneous and sensory-evoked activity in the gamma frequency range. Simultaneous recordings in Gr layer of two neighboring barrel columns revealed that EGOs are restricted to the principal barrel (n = 13) (P5 to P7).
We further addressed the development of activity transfer from Gr to the downstream supragranular (SG) layers and of horizontal synchronization by gamma oscillations in the neighboring columns. During the first postnatal week, PW-evoked responses in SG layers were weak and virtually no response was seen to adjacent whisker (AW) stimulation in either Gr or SG layers. This is in keeping with the emergence of suprathreshold Gr to SG and horizontal connections only from the second postnatal week. From the end of the second postnatal week onward, power in the gamma frequency band in Gr and SG layers progressively increased, and gamma oscillations started to synchronize units in the neighboring columns. Unlike EGOs, these later-emerging “adult” gamma oscillations were not time-locked to the stimulus and were maximal in SG layers. Simultaneous recordings from neighboring barrel columns in P19 to P33 rats (n = 6) revealed strong horizontal gamma synchronization of units. Thus, during development, sensory-evoked gamma activity switches from transient input-specific “vertical” EGOs to “horizontal” gamma oscillations synchronizing activity in neighboring cortical columns. The switch is characterized by a developmental gap between these two forms of gamma activity: EGOs disappear around P8, whereas adult gamma activity gradually builds up along with a development of the active cortical state, manifested by an increase in background activity, and with the development of explorative behaviors and active whisking that starts at P11 to P13.
EGOs primarily result from a gamma-rhythmic excitatory input to Gr cells, which constitutes the only drive for EGOs during the first postnatal days. Local inhibitory circuits are progressively recruited into EGOs only at the end of the first postnatal week.
The two facets of perisomatic inhibition—feed-forward inhibition and gamma synchronization—show remarkably similar developmental profiles during the first postnatal week.
Simultaneous recordings from topographically aligned loci in the ventral posterior medial (VPM) nucleus of the thalamus and corresponding cortical column (n = 9) (P5 to P7) revealed PW-evoked gamma-rhythmic VPM MUA responses (peak frequency 48 ± 1 Hz), strongly coherent with cortical EGOs. Thalamic units showed strong phase modulation relative to the cortical EGOs (resultant vector = 0.24) such that they fired 7 ±1 ms ahead of Gr cells. This thalamocortical binding was maintained for eight EGO cycles, indicating a multiple replay of a sensory input in topographic thalamocortical microcircuits. Interestingly, blockade of intrathalamic inhibition suppressed cortical EGOs at P2 to P4 (n = 5) (fig. S9), suggesting that the generation of thalamic gamma activity involves synchronization driven by the reticular nucleus.
Our findings suggest the following network model. Sensory input from a whisker activates an inhibition-based gamma oscillator in the thalamic barreloid, which imposes topographic feed-forward synchronization in the corresponding cortical barrel. Cortical interneurons then become involved in EGOs in an age-dependent manner. Until ~P5, EGOs are independent of cortical inhibition. Starting from P5, along with the development of feed-forward inhibition, interneurons are recruited and support EGOs by controlling runaway recurrent cortical excitation. Thus, during the first postnatal week, EGOs undergo evolution from a primitive form of cortical activity passively following a thalamic oscillator, to a more complex interactive model in which an active cortical oscillator, by virtue of emerging inhibition, starts to support gamma oscillations.
The first postnatal week is also characterized by an enhanced plasticity of thalamocortical connections. From a synaptic plasticity standpoint, EGOs provide repetitive synchronization of thalamic and cortical neurons, thus creating conditions for potentiation of the topographic thalamocortical connections. Indeed, 30 artificial EGOs (aEGOs), mimicked by pairing subthreshold gamma-rhythmic (50 Hz) thalamic input with action potentials in Gr neurons in thalamocortical slices, resulted in long-lasting potentiation of thalamocortical EPSPs by 23 ± 1% (n = 9) (P4 to P6). In contrast, 30 artificial spindle-bursts (10 Hz) or rhythmic pairing at 0.5 Hz induced a depression or no change in EPSPs, respectively.
In summary, we show that EGOs are a characteristic activity pattern transiently expressed in the developing rat barrel cortex during the critical period for activity-dependent plasticity in thalamocortical synapses. In contrast to the inhibition-based “adult” gamma oscillations that emerge at the end of the second postnatal week and enable horizontal synchronization, EGOs are primarily driven by gamma-rhythmic excitatory thalamic input and provide vertical synchronization between topographically aligned thalamic and cortical neurons. Multiple replay of sensory input in the thalamocortical synapses during EGOs may allow thalamic and cortical neurons to be woven into vertical topographic functional units before the development of horizontal binding and other integrative cortical functions subserved by “adult” gamma oscillations in mature brain.
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