Abstract:Neuronal stimulus selectivity is shaped by feedforward and recurrent excitatory-inhibitory interactions. In the auditory cortex (AC), parvalbumin- (PVs) and somatostatin-positive (SOMs) inhibitory interneurons differentially modulate frequency-dependent responses of excitatory neurons. Responsiveness of neurons in AC to sounds is furthermore dependent on stimulus history. We found that inhibitory effects of SOMs and PVs diverged as a function of adaptation to temporal repetition of tones. Prior to adaptation, … Show more
“…On the other hand, it cannot be ruled out that after spending longer periods in the absence of SSTi, changes in the locomotor, emotional or pain sensitivity parameters would take place. As mentioned before, SSTi are regulators of adaptive properties (Natan et al., ) and their loss for longer periods, although speculative, could result in escalating behavioural changes over time.…”
Section: Discussionmentioning
confidence: 95%
“…*p < .05, **p < .01. [Colour figure can be viewed at wileyonlinelibrary.com] of adaptive properties (Natan et al, 2017) and their loss for longer periods, although speculative, could result in escalating behavioural changes over time.…”
The striatum is mainly composed by medium spiny neurons (95 %) (MSNs). Although outnumbered, in other brain regions such as the hippocampus and the cortex, somatostatin interneurons (SSTi) are known to control and fine‐tune the activity of principal cells. This information is still fragmented for the striatum. Here, we questioned the striatal functional consequences of the selective ablation of SSTi in the striatum at the behavioural and cellular levels. We identified increased excitability coupled with decreased distal spine density in MSNs from SSTi‐ablated mice. Although the ethological behavioural analysis did not reveal differences between the groups, SSTi‐ablated mice were significantly more sensitive to the locomotor effects of cocaine without changes in motivation. This was accompanied by increased expression of the dopamine transporter (DAT) in the ventral striatum. Altogether, we show that SSTi are important players in the maintenance of MSN excitability and spine density impacting on mechanisms towards hyperdopaminergic states.
“…On the other hand, it cannot be ruled out that after spending longer periods in the absence of SSTi, changes in the locomotor, emotional or pain sensitivity parameters would take place. As mentioned before, SSTi are regulators of adaptive properties (Natan et al., ) and their loss for longer periods, although speculative, could result in escalating behavioural changes over time.…”
Section: Discussionmentioning
confidence: 95%
“…*p < .05, **p < .01. [Colour figure can be viewed at wileyonlinelibrary.com] of adaptive properties (Natan et al, 2017) and their loss for longer periods, although speculative, could result in escalating behavioural changes over time.…”
The striatum is mainly composed by medium spiny neurons (95 %) (MSNs). Although outnumbered, in other brain regions such as the hippocampus and the cortex, somatostatin interneurons (SSTi) are known to control and fine‐tune the activity of principal cells. This information is still fragmented for the striatum. Here, we questioned the striatal functional consequences of the selective ablation of SSTi in the striatum at the behavioural and cellular levels. We identified increased excitability coupled with decreased distal spine density in MSNs from SSTi‐ablated mice. Although the ethological behavioural analysis did not reveal differences between the groups, SSTi‐ablated mice were significantly more sensitive to the locomotor effects of cocaine without changes in motivation. This was accompanied by increased expression of the dopamine transporter (DAT) in the ventral striatum. Altogether, we show that SSTi are important players in the maintenance of MSN excitability and spine density impacting on mechanisms towards hyperdopaminergic states.
“…Linear fits across frequencies. Linear fits were calculated using linear regression (fitlm.m; MATLAB) over 50 data points, one for each of the 50 frequencies tested (Natan et al, 2017b). The 50 data points were separately calculated as the mean FR over all repeats of each frequency.…”
The extensive feedback from the auditory cortex (AC) to the inferior colliculus (IC) supports critical aspects of auditory learning, but has not been extensively characterized. Furthermore, it remains unknown whether and how intra-cortical processing of auditory information propagates to earlier stages in the auditory pathway. Previous studies demonstrated that responses of neurons in IC are altered by focal electrical stimulation and pharmacological inactivation of auditory cortex, but these methods lack the ability to selectively manipulate the activity of projection neurons. Combining viral technology with electrophysiological recordings, we measured the effects of selective optogenetic activation or suppression of cortico-collicular feedback projections on IC responses to sounds. Activation of cortico-collicular feedback generally increased spontaneous activity and decreased stimulus selectivity in IC, whereas suppression of the feedback did not affect collicular activity. To further understand how microcircuits in the auditory cortex may control collicular activity, we tested the effects of optogenetically modulating different cortical neuronal subtypes, specifically parvalbumin-positive (PV) and somatostatin-positive (SOM) inhibitory interneurons. We found that, despite strong effects on sound-evoked responses across the layers of AC, activating either type of interneuron did not affect IC sound-evoked activity. However, suppression of SOMs, but not PVs, weakly increased spontaneous activity in IC. These findings suggest that shaping of sound responses mediated by cortical inhibition does not affect sound processing in IC. Combined, our results identify that activation of excitatory projections, but not inhibitory-driven increases in cortical activity, affects collicular sound responses.
Significance StatementDescending projections from the auditory cortex to the auditory midbrain, the inferior colliculus, have been shown to play a critical role in auditory learning and behavior. However, little is known about the details of how this direct feedback shapes neuronal responses to sounds in the inferior colliculus. We found that direct activation of cortico-collicular feedback increased spontaneous and modulated sound-evoked activity in the inferior colliculus. Interestingly, modulation of inhibitory interneuron activity, thereby increasing or decreasing excitatory neuronal activity in the auditory cortex, did not affect sound responses in the inferior colliculus. This work offers evidence that auditory cortex shapes sound responses in the inferior colliculus via direct feedback independently of the activity of cortical inhibitory interneurons.
“…This non-uniform distribution of selectivities suggested that the two cell clusters differentially process spatiotemporal information. FFI mediated by rapid synaptic activation of PVs (D'Souza et al, 2016) is a circuit motif shown to shape the temporal sensitivity of PNs in auditory cortex independent of stimulus adaptation (Li et al, 2014;Natan et al, 2017). Because the strength of FFI depends on the excitatory input to PNs and PVs and the latter's inhibition of PNs (Atallah et al, 2012), we compared the strength of excitatory inputs to patches and interpatches from different thalamocortical and intracortical pathways to L2/3 neurons in V1.…”
Section: Module-and Pathway-specific Synaptic Strengths Of Inputs To mentioning
Whether mouse visual cortex contains orderly feature maps is debated. The overlapping pattern of geniculocortical (dLGN) inputs with M2 muscarinic acetylcholine receptor-rich patches in layer 1 (L1) suggests a non-random architecture. Here, we found that L1 inputs from the lateral posterior thalamus (LP) avoid patches and target interpatches. Channelrhodopsin-assisted mapping of EPSCs in L2/3 shows that the relative excitation of parvalbumin-expressing interneurons (PVs) and pyramidal neurons (PNs) by dLGN, LP and cortical feedback are distinct and depend on whether the neurons reside in clusters aligned with patches or interpatches.Paired recordings from PVs and PNs shows that unitary IPSCs are larger in interpatches than patches. The spatial clustering of inhibition is matched by dense clustering of PV-terminals in interpatches. The results show that the excitation/inhibition balance across V1 is organized into patch and interpatch subnetworks which receive distinct long-range inputs and are specialized for the processing of distinct spatiotemporal features. S1), and measured EGFP intensity in patches (top 3 rd ) and interpatches (bottom 3 rd ). We then normalized the pixel values in interpatches to the mean intensity in patches and plotted the counts in different intensity bins. We found that the fluorescence intensity in patches was 2.1 ± 0.024fold (p = 8x10 -18 , Komolgorov-Smirnov test [KS]) higher in patches than interpatches ( Figure 1D). Similar to our previous findings, patches and interpatches in L1 were 60-80 µm wide and their centroids were 120-140 µm apart. dLGN projections to L4, and 5/6 appeared uniform (data not shown). Inputs to L1 from the LP thalamus exhibited a strikingly different pattern, showing 1.6 ± 0.14-fold (p = 1.33x10 -4 , KS) stronger projections to M2-interpatches ( Figure 1E-H).Simultaneous tracing of dLGN and LP inputs with AAV2/1hSyn.tdTomato.WPRE.bGH and AAV2/1.hSyn.EGFP, respectively, confirmed the interdigitating pattern of projections from primary and higher order thalamic nuclei, showing denser LP input to interpatches (p = 7.95 x 10 -4 , KS) ( Figure 1I-M).
Clustering of intracortical inputs to L1 of V1We next compared feedback projections from the higher visual cortical ventral stream lateromedial area, LM, to V1 with inputs from the dLGN. Double viral tracings from the dLGN (AAV2/1.hSyn.EGFP) and LM (AAV2/1hSyn.tdTomato.WPRE.bGH) showed that inputs from both sources overlapped in presumtive M2+ patches of L1 ( Figure 1A-C; 2A). Quantitative analysis showed that LM inputs to patches were 1.7 ± 0.05-fold denser than to interpatches (p = 1.45x10 4 , KS) ( Figure 2B). We have shown previously that inputs from the dorsal stream anterolateral area, AL, terminate in M2+ patches (Ji et al., 2015), raising the question whether M2+ patches are the preferred targets of cortical feedback. To address this, we traced the connections to V1 from the posteromedial area, PM, another member of the dorsal stream (Wang et al. 2012). We found that inputs from PM were non-uniform, overlapped i...
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