Rethinking Sensory Information Processing: The Essential Role of Astrocytes

ABSTRACT

One of the most fundamental abilities of the nervous system is to perceive, integrate, and process sensory inputs from the external environment. This physiological ability, known as sensory information processing, has been extensively studied using diverse experimental models, ranging from in vivo vertebrates and invertebrates to in vitro and computational approaches. Most of these seminal studies have primarily focused on neuronal components, providing critical insights into the principles of excitation and inhibition circuit dynamics and anatomical wiring. However, studies in the last decade have shed light on the important role of astrocytes in sensory information processing. The astrocytic effect on controlling the strength and gain of sensory neuronal responses is particularly evident in awake and freely moving animals, where their modulation has a direct influence on behavioral output, positioning them as cell targets to understand sensory processing as a whole in brain (dys)function. In this review, we draw attention to new research that casts doubt on the conventional neurocentric theories of sensory processing and highlights the growing influence of astrocytes on how sensory processing is shaped across modalities.

In this review, we discuss recent advances highlighting the emerging roles of astrocytes in sensory information processing. We review how astrocytes are anatomically integrated within distinct sensory systems, how they are activated by specific external stimuli, and how their modulation influences the output of sensory neurons to shape behavioral responses. By outlining both shared and modality‐specific mechanisms, we provide an updated perspective on astrocytic contributions to sensory integration, emphasizing their pivotal role in bridging cellular signaling and systems‐level brain function.

Abbreviations

[K⁺]ₑ

extracellular potassium concentration

IP3R2

koinositol‐1,4,5 triphosphate receptor‐type 2 knockout mice

ATP

adenosine triphosphate

Ca²⁺

calcium

DREADD

Designer Receptors Exclusively Activated by Designer Drugs

GABA

Gamma‐aminobutyric acid

GLT‐1

glutamate transporter 1

hM3Dq

modified form of the human M3 muscarinic (hM3) receptor

hM4Di

modified form of the human M4 muscarinic (hM4) receptor

LGN

lateral geniculate nucleus

M/T

Mitral and tufted neurons in the olfactory bulb

mGluR2

metabotropic glutamate receptor subtype 2

mGluR5

metabotropic glutamate receptor subtype 5

NB

nucleus basalis

NE

norepinephrine

NMDA

N‐methyl‐D‐aspartate receptor

nRT

reticular thalamic nucleus

OB

olfactory bulb

OG

olfactory glomeruli

OSN

olfactory sensory neurons

PV

parvalbumin inhibitory neurons

RNA

Ribonucleic acid

S1

primary somatosensory cortex

SC

superior colliculus

SLC22A3

Solute Carrier Family 22 Member 3

SOM

somatostatin inhibitory neurons

TTX

tetrodotoxin

V1

primary visual cortex

VBC

ventral basal complex

VTA

ventral tegmental area

1. Overview of Sensory Information Processing

Sensory inputs coming from the external world (i.e., vision, hearing, touch, taste and smell; Lee et al. ²⁰¹⁶; Sabri and Arabzadeh ²⁰¹⁸) or internal organs (i.e., visceral sensations; Ran et al. ²⁰²²; Wang and Chang ²⁰²⁴) are perceived, integrated, and computed by multiple sensory systems to ensure survival and environmental adaptation. The hierarchical structure of the sensory information processing starts with the detection of physical or chemical sensory inputs by specialized receptors that convert these inputs into electrical signals encoding stimuli features. Then, through specific pathways (e.g., optic or auditory nerve, ascending tracts of the spinal cord), the transduced signal is relayed to the thalamus before reaching primary sensory cortical areas (Sherman 2017). Within sensory cortices, the specific aspects of the input will be processed to generate a refined and shaped representation of the information, which is then transmitted to higher‐order brain regions for multimodal integration, allowing for perception, decision‐making, and response planning. Disruptions at any stage of sensory information processing in both the developing and adult nervous systems can lead to sensory pathologies such as those seen in autism spectrum disorder, neuropathic pain, or sensory processing disorder (Falcão et al. 2024; Huang et al. ²⁰¹⁹; Kourdougli et al. ²⁰²³)—all of them challenging to diagnose and treat, highlighting the complexity of sensory integration in brain function and the importance of studying these systems.

Historically, sensory processing studies have predominantly focused on neuronal pathways and components, emphasizing how the different features of the fast and spatially constricted synaptic circuits allow encoding, transmission, and interpretation of sensory signals (Rosa et al. 2016; Wood et al. ²⁰¹⁷). Also, the slowly acting neuromodulation encoding internal state information is considered a complementary system favoring and shaping neuronal responses to sensory inputs (Rodenkirch et al. 2019; Rodenkirch and Wang ²⁰²⁴). In addition to these two parallel and complementary systems, the non‐neuronal cells, astrocytes, have emerged in the last decade as key elements in sensory information processing (Lines et al. 2020; Miguel‐Quesada et al. ²⁰²³; Ung et al. ²⁰²⁰; Visser et al. ²⁰²⁴). They do so by controlling synaptic activity, regulating blood flow, and influencing neuronal excitability that ultimately affects gain and input control of the neuronal network (Miguel‐Quesada et al. ²⁰²³). The astrocytic capacity to dynamically adjust the network sensitivity to incoming inputs allows scaling of the neuronal output response across different contexts and input intensities (Miguel‐Quesada et al. ²⁰²³). This is important in the context of the downstream signaling modulating, for example, the precision of motor responses during sensorimotor integration to give rise to adequate behavior (Ferezou et al. 2007; Matyas et al. ²⁰¹⁰) (Figure 1). It may also influence cortical–subcortical projections (i.e., towards thalamus, superior colliculus, striatum, limbic structures) leading to modulation of sensory refinement related to perception, attention, behavior, and internal states (Canedo and Aguilar 2000; Krauzlis et al. ²⁰¹³; Sherman ²⁰¹⁷). In addition, it has been recently postulated that astrocytes act as an integrator between arousal states (neuromodulation) and sensory information (synaptic activity) (see review Rasmussen et al. ²⁰²³), challenging the traditional neurocentric view and revealing a more complex and integrative model of sensory processing. In this review, we will highlight key aspects and recent findings on how astrocytes are anatomically wired within sensory systems, how they are activated by specific inputs, and how their modulation influences the output signals from sensory neurons to the resulting behavior. Our goal is to provide an overview of their role in the processing of external sensory inputs, highlighting similarities and differences across sensory modalities (Table 1).

FIGURE 1.

Schematic representation of astrocyte‐mediated modulation of cortical circuit output. Dynamic alterations in astrocyte network activity influence neuronal population responses, thereby refining sensorimotor integration and regulating the strength and pattern of corticofugal projections to subcortical structures.

TABLE 1.

Summary of the astrocytic contribution to sensory information processing across different systems and modalities.

System	Astrocyte modulation at cellular and circuit level	Behavior control	Ref.
Visual system	Astrocytic response highly dependent on brain state and neuromodulation level Regulation of inhibitory and excitatory spontaneous firing Formation of retinotopic map at the superior colliculus	Reduced visual orientation and direction selectivity (V1) by (opto)genetic modulation of astrocyte activation Impaired light‐induced arrest behavior by astrocyte gap junction disruption	Schummers et al. 2008 Chen et al. 2012 Perea et al. 2014 Visser et al. 2024
Olfactory system	OG astrocyte coupling network depends on neuronal activity Regulation of neuronal calcium response Control of olfactory lateral inhibition and gene expression related to odor maps and release/uptake of neuromodulators	Contribute to odor detection performance on olfactory learning task Shape odor contrast and facilitates discrimination	Roux et al. 2011 Ung et al. 2020 Ung et al. 2021 Sardar et al. 2023
Somatosensory system	Regulation of spontaneous E:I balance and gamma frequency oscillations Control of input and response gain (dynamic range) of S1 neuronal networks Thalamic tonic inhibitory tone	Contribute to tactile and thermal threshold detection Acuity of tactile discrimination	Lines et al. 2020 Miguel‐Quesada et al. 2023 Kwak et al. 2020
Auditory system	Correlated neuron‐astrocyte calcium responses		Kellner et al. 2021

2. Visual System

The visual system is one of the most widely used sensory systems to study information processing due to its well‐defined anatomical and functional organization (e.g., retina, LGN, V1, and higher visual areas) and the ability to apply its natural stimuli. By using the visual system as a model, neuroscientists have uncovered many aspects of how astrocytes influence visual processing from the retina to the cortex, including synaptic transmission, neuronal excitability, and network activity. Pioneering in vivo studies in the primary visual cortex (V1) of ferrets first demonstrated that V1 astrocytes respond to visual stimuli with robust increases in intracellular calcium, tuned to orientation and spatial frequency (Schummers et al. 2008). In these early studies, the temporal dynamics of the visually evoked neuronal responses (e.g., magnitude and duration) were highly affected by pharmacological inhibition of astrocyte glutamate clearance, evidencing their contribution to visual processing through modulation of neuronal excitability. However, discrepancies were found in further in vivo studies using anesthetized mice in which astrocyte response to visual stimulation showed weak, unreliable, or sparse activity (Asada et al. 2015; Bonder and McCarthy ²⁰¹⁴; Paukert et al. ²⁰¹⁴). Nonetheless, with the use of imaging techniques in awake, behaving animals, it was clear that the astrocytic unresponsiveness to visual stimulation is related to brain state level and neuromodulatory conditions usually observed in sedated mice. In anesthetized mice, while V1 neurons reliably responded to visual inputs, astrocytes initially showed only global activity unrelated to the stimuli (Sonoda et al. 2018). However, blocking alpha 1‐adrenergic receptors—which mediate neuromodulation from the locus coeruleus—unmasked the astrocytic visual responses. Another demonstration of the strong influence of neuromodulation on V1 astrocyte responsiveness was demonstrated by electrical stimulation of the nucleus basalis (NB) to enhance cholinergic signaling onto the visual cortex (Chen et al. 2012). In this study, the potentiation of the direction and orientation selectivity of visual cortical neurons to NB stimulation was drastically impaired in conditional inositol‐1,4,5 triphosphate receptor‐type 2 knockout mice (IP3R2‐ko) lacking astrocyte somatic calcium activation. Besides these experiments using strategies to alter neuromodulation, it was also shown that V1 astrocytes in awake mice show calcium responses to visual stimulation (Paukert et al. 2014; Slezak et al. ²⁰¹⁹). Nonetheless, this awake activity was also strongly dependent on behavioral state and norepinephrine level, with astrocytes showing stronger activity during locomotion and little activity during stationary resting (Paukert et al. 2014; Slezak et al. ²⁰¹⁹). Therefore, in the visual cortex, the detection threshold of astrocytes to a stimulus appears to have a much stronger contribution of internal state compared to other sensory systems (López‐Hidalgo et al. ²⁰¹⁷). After the description that V1 astrocytes were responsive to visual stimulation and their activity was strongly regulated by the level of neuromodulators, further studies delved into the role of astrocytes in the processing of sensory visual inputs. For example, by using optogenetics stimulation targeting V1 astrocytes, it was demonstrated that these cells control the basal tone of V1 cortical activity by modulating the spontaneous firing rate of PV+, SOM+, and excitatory neurons (Perea et al. 2014). Furthermore, optogenetic astrocyte stimulation led to reduced orientation and direction selectivity in mice, evidencing their contribution to information processing in the visual cortex. The optogenetic effects may result from a direct astrocytic gliotransmission mechanism influencing neuronal excitability. However, it is important to note that channelrhodopsin‐mediated activation of astrocytes significantly elevates extracellular potassium levels [K⁺]_e, which could introduce indirect effects on neuronal activity, as reported by Octeau et al. (2019).

Astrocytes were also shown to have a crucial role in visual processing at the level of the retinorecipient layer of the superior colliculus (SC) (Visser et al. 2024), a structure in the mammalian midbrain that transforms multisensory information into motor outputs. By their gap junction connected network, astrocytes allow the formation of a retinotopic map at the SC to process visually arriving inputs. Indeed, genetic disruption of the gap junction mediated astrocytic map led to the impairment of the light‐induced arrest behavior assay, a SC‐dependent behavior test that measures the temporary suspension of locomotion upon sudden flashes of light. Therefore, astrocytes strongly modulate visual sensory processing by affecting the spontaneous excitability of neurons as well as by modulating the circuit refinement of visual maps within the visual system.

3. Somatosensory System

The somatosensory system relies on a well‐structured topographical arrangement that allows the study of the spatiotemporal properties of information processing from four modalities (tactile, proprioception, nociception, and thermal sensation) at distinct anatomical levels (spinal cord, brainstem, thalamus and cortex). At the cortical level, the specialized region of the barrel cortex has been extensively used to characterize the neuronal features of sensory processing related to tactile‐whisker discrimination (Arabzadeh et al. 2003; Castro‐Alamancos ²⁰⁰⁴; Helmchen et al. ²⁰¹⁸). In this sensory area, astrocytes are distributed thoroughly within and between barrels (Houades et al. 2008). Peripheral stimulation of individual whiskers induces strong frequency‐dependent intracellular Ca²⁺ surges in astrocytes mediated mostly by metabotropic glutamatergic receptors, indicating their ability to respond to presynaptic input in a well‐defined somatotopy (Wang et al. 2006). Nonetheless, their evoked responses are restricted to the whisker‐specific column, with none or weak induced activity in neighboring barrels, suggesting a preferential cell circuit arrangement within each receptive field. Similar astrocyte anatomical arrangements and evoked activation patterns are also observed at the somatotopic representation of fore/hindlimbs of the somatosensory cortex (S1), in which electrical limb stimulation induces robust S1 astrocyte activation in a frequency‐ and intensity‐dependent manner (Ghosh et al. 2013; Lines et al. ²⁰²⁰; Miguel‐Quesada et al. ²⁰²³). Additionally, a recent study indicates that a subpopulation of astrocytes within the somatosensory cortex is directly activated by sensory inputs, supporting the idea that astrocytes may serve as direct integrators of sensory information (Stobart et al. 2018). This is particularly relevant in sensory processing as peripheral sensory stimulation activates multiple receptive fields across large body areas—for example, the activation of entire fore/hindlimbs during natural locomotion, or the engagement of all or some whiskers during object exploration. In this case, sensory computation is not restricted to an individual local circuit but requires the connectivity between adjacent networks to appropriately process the information. Therefore, the astrocytic recruitment as a parallel population to neurons may increase the capacity of computation during sensory processing, although further studies will need to closely look for this possibility (Ghosh et al. 2013; Lines et al. ²⁰²⁰; Miguel‐Quesada et al. ²⁰²³).

Another important aspect of S1 is its layered organization, which refines sensory processing by modulating synaptic inputs within each local layering circuit (Douglas and Martin 2004). Therefore, astrocytes may contribute to sensory processing by either modulating the transfer of information or by acting at the synaptic level within each layering circuit. In this context, astrocytic cannabinoid signaling improves the synaptic connectivity across layers within a cortical barrel column (Baraibar et al. 2023). This effect was absent between neurons from different barrels, indicating a focal effect of astrocytes during sensory processing. Astrocytes also modulate individual layering circuits by mediating spike‐timing long‐term depression or experience‐dependent homeostatic plasticity in layer 2/3 neurons through either D‐serine release or intracellular pathways (Andrade‐Talavera et al. ²⁰²⁴; Butcher et al. ²⁰²²). This may play a role in determining the dendritic integration of synaptic inputs as observed in CA1 pyramidal neurons (Bohmbach et al. 2022). Similarly, in vivo astrocytic gain‐ or loss‐of‐function experiments induce a layer‐dependent modulation of the sensory evoked‐neuronal response (Figure 2). Reduced response gain (i.e., magnitude of sensory‐evoked potentials) or input gain (i.e., minimum stimulation to generate a cortical response) of cortical networks to paw stimulation is more prominent in those thalamic recipient layers when compared to other layers (Miguel‐Quesada et al. ²⁰²³). In addition, the excitability of neuronal networks in layer 2/3 in response to continuous sensory stimulation is maintained by natural activation of astrocytes but is perturbed by increasing or decreasing the astrocytic activity (Lines et al. 2020). These results demonstrate that astrocytes control the dynamic range of neuronal network activation across cortical layers to properly compute and transfer arriving inputs.

FIGURE 2.

Cortical astrocytes regulate the dynamic range of neuronal network activation. (A) Schematic representation of ascending sensory pathways projecting to the hindlimb coordinate of the primary somatosensory cortex (S1HL). POm (posterior medial nucleus of the thalamus) and VPL (ventral posterolateral nucleus of the thalamus) represent the thalamic nuclei receiving thermal and tactile information, respectively. Layer (L). (B) Diagram of the in vivo electrophysiological setup used to record sensory‐evoked potentials (SEP) across cortical layers (L) in S1HL. (C) Experimental strategies to modulate astrocyte activity. Astrocyte activation was selectively induced via Gq‐DREADD expression followed by clozapine‐N‐oxide (CNO) intraperitoneal injection in hM3Dq⁽⁺⁾ mice, whereas astrocyte somatic calcium signaling was attenuated in IP₃R2 knockout mice. (D) Impact of astrocytic gain‐of‐function (Gq‐DREADD activation, hM3Dq⁽⁺⁾ = before CNO injection, control condition; hM3Dq⁽⁺⁾ + CNO = following CNO i.p. injection) and loss‐of‐function (IP₃R2^+/+ = littermate wildtype mice; IP₃R2^−/− = knockout mice) manipulations on the magnitude of sensory‐evoked potentials (SEP) recorded in layer 2/3 (L2/3) of S1HL in response to hindpaw electrical stimulation (figure modified from Miguel‐Quesada et al. ²⁰²³, Cell Reports).

The integration and processing of sensory inputs by brain structures of the somatosensory system are highly modulated by the level of spontaneous neuronal activity, neuromodulatory tone, and the behavioral state (Aguilar and Castro‐Alamancos ²⁰⁰⁵; Castro‐Alamancos ²⁰⁰⁴; Lee and Dan ²⁰¹²). Since astrocytes regulate neuronal excitability, their activity in S1 may help fine‐tune sensory processing by maintaining the optimal excitability level during spontaneous activity. In this sense, (Miguel‐Quesada et al. ²⁰²³) showed a reduction in the excitatory tone due to increased inhibition when astrocytes were chemogenetically activated. This led to a drastic disruption of neuronal synchronization across cortical layers during slow‐wave activity, and impaired tactile and thermal threshold detection during sensory behavior (Miguel‐Quesada et al. ²⁰²³). Similarly, decreased glutamatergic activation of astrocytes by NMDA receptors knockdown within the barrel cortex drastically reduced sensory acuity during a whisker‐dependent tactile discrimination task (Ahmadpour et al. 2024). Together, these results demonstrate that astrocytes contribute to sensory discrimination at the somatosensory cortex by modulating synaptic strength, information transfer, and spontaneous neuronal excitability.

The role of astrocytes in sensory processing is not constrained to S1, but it has been studied at the thalamic level (Crunelli et al. 2002; Gould et al. ²⁰¹⁴; Höft et al. ²⁰¹⁴; Parri et al. ²⁰¹⁰) where sensory information is filtered by inhibitory inputs before ascending to the primary somatosensory cortex. Classically, inhibitory neurons from the reticular thalamic nucleus (nRT) were considered the sole source of tonic and phasic thalamic inhibition (Cope et al. 2005). However, astrocytes were later described as an additional thalamic source of tonic GABAergic inhibition (Copeland et al. 2017) contributing to the acuity of tactile discrimination by reducing noise and filtering out non‐relevant inputs (Kwak et al. 2020). Beyond the direct inhibition of the neuronal networks, studies have described that thalamic astrocytes express different receptors, allowing them to sense synaptic activity in the ventral basal complex (VBC) network (Copeland et al. 2017; Gould et al. ²⁰¹⁴; Höft et al. ²⁰¹⁴). For example, astrocytes respond to increased glutamate levels at nearby synapses through NMDA receptors (Ahmadpour et al. 2024), mGluR2 receptors (Copeland et al. 2017) and mGluR5 (Parri et al. 2010). A common outcome of this activation is to reduce overall nRT inhibition while increasing local excitability. This serves to increase the contrast between a more excited (by a disinhibition mechanism) principal receptive field, while the secondary receptive field remains inhibited. In contrast, while ionotropic and metabotropic GABA receptors have been described in thalamic VBC astrocytes, results about their role in sensory processing are less consistent across different works (Gould et al. 2014; Höft et al. ²⁰¹⁴). Therefore, future work is required to determine how astrocytes respond to GABA increases to modulate closer synaptic activity and neuronal networks.

The contribution of astrocytes to sensory information processing was also recently explored at the level of the dorsal horn of the spinal cord, where the sensory integration for different modalities takes place. In this sense, astrocytes in superficial layers 1 and 2 of the dorsal horn show a profile closer to nociception sensory integration, while astrocytes located in layer 3 could be related to tactile processing (Kronschläger et al. 2021). Importantly, these authors finally remark on the idea of the heterogeneity of astrocytes in relation to anatomical location and functional role. This could be important considering nociception, which is a different sensory modality of the somatosensory system, and it is first processed by spinal cord dorsal horn circuits. In this sense, reduced astrocytic gliotransmission in the dorsal horn leads to a decreased mechanical nociceptive threshold (Foley et al. 2011). Therefore, a dysregulation of astrocyte activity in the dorsal horn could be involved in the development of somatosensory dysfunctions such as chronic pain and itch (Ji et al. 2019). Moreover, different works indicate that astrocytes are involved in other processes associated with chronic pain, such as neuroinflammation; however, this goes beyond the scope of this review focusing on sensory processing.

4. Olfactory System

The olfactory system is a highly adaptive and complex sensory system that enables odor detection, discrimination, and processing. In addition, it has direct connections to emotional and memory centers, making it unique compared to other sensory modalities. Regarding sensory processing, after peripheral receptors activation in the nasal cavity, odor signals travel towards the olfactory bulb (OB) to activate the different olfactory glomeruli (OG) representing the functional units where olfactory processing initially occurs (McIntyre et al. ²⁰¹⁷). Within each OG, astrocytes are abundantly present, forming a confined and connected network that overlaps neuronal organization. Such an arrangement is highly dependent on the level of neuronal excitability, as the presence of TTX to block neuronal activity or sensory deprivation significantly reduces the astrocytic coupling within OG (Roux et al. 2011). These seminal experiments showed that by sensing [K⁺]_e generated by neuronal activity, astrocytes could control the level of their connected net and therefore impact the first relay of the olfactory information processing at the glomerular level. After this initial description of the defined coupling structure, OG astrocytes were described to display robust mGluR5‐mediated Ca²⁺ surges following in vivo odor stimulation in juvenile mice (Otsu et al. 2015). Such OG astrocyte‐evoked activity displayed a rapid onset but was only appreciated in response to extremely strong activation of both olfactory sensory neurons and the postsynaptic glomerular network. The latter resembles the pattern of astrocyte activity at the primary somatosensory cortex and the need for high‐frequency stimulation to induce a network activation of astrocytes in anesthetized animals (Lines et al. 2020; Miguel‐Quesada et al. ²⁰²³). In addition, the evoked activity was restricted to astrocytic processes and absent in the soma, suggesting a more localized and restricted actions on synapses and neurovascular coupling, both important aspects of sensory processing.

Outside the OG, astrocytes within the domains of mitral and tufted cells—the main excitatory neuron population in the OB that relays odor information to the piriform cortex—are also activated in response to in vivo odor stimulation, forming an odor‐response map (Ung et al. 2020). In this context, activating astrocytes with hM3Dq DREADD in the olfactory bulb decreased neuronal Ca²⁺ responses to odor stimulation and improved performance in a Go/NoGo associated olfactory learning task (Ung et al. 2020). The decreased neuronal activity following astrocyte DREADD activation was suggested to be an additional mechanism of lateral inhibition within the OB. However, it is still unclear whether this is a direct effect of astrocytes on M/T neurons or through an indirect modulation via inhibitory neurons affecting excitatory cells.

In contrast, stimulation of hM4Di DREADD in OB astrocytes caused an increase in neuronal Ca²⁺ odor responses but resulted in less accurate odor detection performance (Ung et al. 2021). These revealed that astrocytes in the surroundings of these excitatory neurons, outside the OG, have a direct impact on odor processing by changing their detection threshold. Together, these results show that astrocytes within the olfactory glomeruli and those near mitral/tufted neurons play different but complementary roles in olfactory processing. In summary, the astrocytic OG syncytium interacts closely with OSN terminals and glomerular interneurons to modulate the strength of incoming sensory inputs. They do that by affecting synaptic transmission and plasticity through the release of bioactive molecules such as glutamate, ATP, D‐serine, as well as by controlling the extracellular ion concentration and the level of lateral inhibition. All of these actions within the OG have the primary function of shaping odor contrast and facilitating odor coding and discrimination. On the other side, astrocytes near mitral/tufted neurons—the next step of processing after OG—regulate the OB output by influencing synaptic transmission and helping in the sensory integration toward higher‐order circuits.

Olfactory sensory detection and discrimination has been found to be highly affected by norepinephrine (NE) inputs from the locus coeruleus, improving signal‐to‐noise ratio and neuronal synchronization in mitral cells (Escanilla et al. 2010; Manella et al. ²⁰¹⁷). Until very recently, NE's effects were thought to be related to its direct action on neuronal activation. However, this is now at odds with growing evidence that NE modulates neuronal activity through its binding to adrenergic receptors in astrocytes (Wahis et al. 2024; Wang et al. ²⁰²³). Therefore, as observed in other systems, it is plausible that astrocytes might be implicated in the NE effect on odor processing, a possibility that will need to be further confirmed in mice. Corroborating this possibility, previous results from Drosophila showed a strong neuromodulatory effect of astrocytes in odor processing. In this case, the in vivo release of tyramine and octopamine from neurons, two neuromodulators linked to arousal and aggression in insects and considered to be functionally equivalent to NE in mammals, triggered synchronous Ca²⁺ activity in astrocytes, and their loss‐of‐function profoundly impaired olfactory‐driven chemotaxis (Ma et al. 2016).

Besides the contribution of astrocytes to olfactory processing by modulation of neuronal synaptic activity and connected networks, astrocytes also regulate gene expression and neurotransmitter production within OG to impact processing (Ung et al. 2021). Adult mice undergoing specific deletion of the transcription factor Sox9 in OB astrocytes presented aberrant odor maps, increased OSN innervation, and a reduction in both evoked action potentials firing and postsynaptic currents in M/T neurons. In addition, the genetic modulation of astrocytes also induced changes in gene expression profiles as a reduction of GLT‐1 and reduced glutamate transporter currents leading to decreased levels of odor detection thresholds and discrimination. In this line, a recent study identified a neuronal activity‐inducible astrocyte gene that influences sensory processing in the olfactory bulb (Sardar et al. 2023). In this study, the authors used Gq‐DREADDs to in vivo stimulate neurons and observed an increased expression of the Slc22a3, a membrane transport protein expressed by astrocytes involved in the release and uptake of neuromodulators including serotonin, dopamine, and NE. Then, by doing a selective knockout of Slc22a3 in astrocytes, the authors observed a significant reduction in olfactory detection and discrimination. Therefore, in the olfactory system, astrocytes highly contribute to information processing by controlling the activity of the different neuronal cells responding to odor stimuli by means of threshold detection and discrimination. However, further studies will need to reveal the mechanism(s) that are precisely controlling odor integration and processing.

5. Auditory System

The auditory system is responsible for detecting, processing, and interpreting sounds around our body. In this way, and in common with other sensory systems, the main features are spatial location of sounds, its intensity, and duration. This system shows a huge complexity in the information processing as it takes at least 5 nuclei/structures in the brainstem and midbrain to reach the thalamus (cochlear nuclei, medial nucleus of trapezoid body, superior olive, nucleus of lateral lemniscus and the inferior colliculus) (Kohrman et al. 2021; Purves et al. ²⁰⁰¹). Later, information reaches the medial geniculate nucleus in the thalamus and finally reaches the auditory cortex. The role of astrocytes in different structures of the auditory system has been described mainly during development, for example, in the medial nucleus of trapezoid body (Kohrman et al. 2021), the inferior colliculus, and auditory cortex (Kellner et al. 2021). In more detail, Kellner et al. ²⁰²¹ demonstrated that astrocytic calcium waves observed during development (i.e., prior to the onset of hearing) are limited to this period, but more importantly, they do not find astrocytic activation in response to sensory (auditive) inputs in the mature cortical system. These findings are in consonance with the visual cortex showing astrocyte activity only during periods of heightened arousal, when norepinephrine is released (Paukert et al. 2014; Slezak et al. ²⁰¹⁹). In contrast, a recent publication, using single‐nucleus RNA sequencing, has identified four types of astrocytes in the auditory cortex, from which two show genetic profiles consistent with astrocyte‐neuron interaction (Aydin et al. 2024). Similar to findings in the somatosensory system regarding the role of astrocytes in nociception, most studies on the auditory system focus on pathological conditions such as tinnitus, neuroinflammation, and other auditory problems, which are outside the scope of this review. Therefore, it is clear that studies regarding how astrocytes contribute to auditory information processing are still widely open, and more studies will need to address such questions.

6. Conclusions Remarks

One important aspect that future studies must address is the role of astrocytes in multisensory integration, especially when investigating sensory processing in awake, freely moving animals. Sensory information processing is not an isolated mechanism within specific brain regions but is instead highly influenced by the integration of inputs from other sensory systems and the activation of neuromodulatory regions such as locus coeruleus, nucleus basalis, or VTA. This is particularly relevant for astrocytes, which, as highlighted in this review, are strongly susceptible to neuromodulatory signals. Their influence on neuronal processing may therefore be significantly affected by cross‐modal interactions, brain state, and context (Oliveira and Araque 2022; Reitman et al. ²⁰²³). Additionally, it remains unclear whether astrocytes independently compute sensory information as a secondary processing layer or if their role is primarily centered on modulating neuronal network activity through feedback mechanisms. Moreover, emerging evidence suggests that astrocyte activation in response to excitatory inputs is not spatially homogeneous but rather occurs in distinct ensembles that can modulate behavioral outputs (Serra et al. 2025; Williamson et al. ²⁰²⁵). These findings challenge the traditional view of astrocyte activation as a uniform and passive process, suggesting instead that astrocytes play a more dynamic and functionally relevant role in sensory information processing that will need further studies.

Author Contributions

Juliana M. Rosa: conceptualization, funding acquisition, resources, visualization, writing – original draft, writing – review and editing. Juan Aguilar: conceptualization, funding acquisition, visualization, writing – original draft, writing – review and editing.

Conflicts of Interest

The authors declare no conflicts of interest.

Peer Review

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer‐review/10.1111/jnc.70113.

Data Availability Statement

The authors have nothing to report.