Electrolytic Lesions Research Articles

Role of the Nucleus Accumbens in Signaled Avoidance Actions.

Animals, humans included, navigate their environments guided by sensory cues, responding adaptively to potential dangers and rewards. Avoidance behaviors serve as adaptive strategies in the face of signaled threats, but the neural mechanisms orchestrating these behaviors remain elusive. Current circuit models of avoidance behaviors indicate that the nucleus accumbens (NAc) in the ventral striatum plays a key role in signaled avoidance behaviors, but the nature of this engagement is unclear. Evolving perspectives propose the NAc as a pivotal hub for action selection, integrating cognitive and affective information to heighten the efficiency of both appetitive and aversive motivated behaviors. To unravel the engagement of the NAc during active and passive avoidance, we used calcium imaging fiber photometry to examine NAc GABAergic neuron activity in ad libitum moving mice performing avoidance behaviors. We then probed the functional significance of NAc neurons using optogenetics and genetically targeted or electrolytic lesions. We found that NAc neurons code contraversive orienting movements and avoidance actions. However, direct optogenetic inhibition or lesions of NAc neurons did not impair active or passive avoidance behaviors, challenging the notion of their purported pivotal role in adaptive avoidance. The findings emphasize that while the NAc encodes avoidance movements, it is not required for avoidance behaviors, highlighting the distinction between behavior encoding or representation and mediation or generation.

Neuroelectrophysiology-compatible electrolytic lesioning.

Lesion studies have historically been instrumental for establishing causal connections between brain and behavior. They stand to provide additional insight if integrated with multielectrode techniques common in systems neuroscience. Here, we present and test a platform for creating electrolytic lesions through chronically implanted, intracortical multielectrode probes without compromising the ability to acquire neuroelectrophysiology. A custom-built current source provides stable current and allows for controlled, repeatable lesions in awake-behaving animals. Performance of this novel lesioning technique was validated using histology from ex vivo and in vivo testing, current and voltage traces from the device, and measurements of spiking activity before and after lesioning. This electrolytic lesioning method avoids disruptive procedures, provides millimeter precision over the extent and submillimeter precision over the location of the injury, and permits electrophysiological recording of single-unit activity from the remaining neuronal population after lesioning. This technique can be used in many areas of cortex, in several species, and theoretically with any multielectrode probe. The low-cost, external lesioning device can also easily be adopted into an existing electrophysiology recording setup. This technique is expected to enable future causal investigations of the recorded neuronal population's role in neuronal circuit function, while simultaneously providing new insight into local reorganization after neuron loss.

Selective injury of thalamocortical tract in neonatal rats impairs forelimb use: model validation and behavioral effects.

Unilateral brain injury in neonates results in largely contralateral hand function in children. Most research investigating neurorehabilitation targets for movement recovery has focused on the effects of brain injury on descending motor systems, especially the corticospinal tract. However, a recent human study demonstrated that sensory tract injury may have larger effects on dexterity than motor tract injury. To validate that the sensory tract injury impairs dexterity, we modeled the most common site of sensory tract injury in neonates by targeting the thalamocortical tract. In the postnatal day 7 rats, we used three types of lesions to the thalamocortical tract: periventricular blood injection, photothrombotic lesion, and electrolytic lesion. To test the sensitivity and specificity of these techniques, viral tracers were injected into the primary sensory or motor cortex immediately after injury. Electrolytic lesions were the most specific and reproducible for inducing a lesion compared to the other two methods. Electrolytic lesions disrupted 63% of the thalamocortical tract, while sparing the adjacent corticospinal tract in the internal capsule. To measure the impact on dexterity, the cylinder exploration and pasta handling tests were used to test the changes of forelimb use at 8 weeks after injury when the rats reached maturity. Lesions to the thalamocortical tract were associated with a significant decrease in the use of the contralateral forelimb in the cylinder task, and the degree of impairment positively correlated with the degree of injury. Overall, specific sensory system lesions of the thalamocortical tract impair forelimb use, suggesting a key role for skilled movement.

The Neuroanatomical Basis of the 5-HT Syndrome and Harmalineinduced Tremor.

The 5-HT syndrome in rats is composed of head weaving, body shaking, forepaw treading, flat body posture, hindlimb abduction, and Straub tail. The importance of the brainstem and spinal cord for the syndrome is underlined by findings of 5,7-dihydroxytryptamine (5,7-DHT)-induced denervation supersensitivity in response to 5-HT-stimulant drugs. For head weaving and Straub tail, supersensitivity occurred when the neurotoxin was injected into the cisterna magna or spinal cord, for forepaw treading in cisterna magna, and for hindlimb abduction in the spinal cord. Although 5,7- DHT-related body shaking increased in the spinal cord, the sign decreased when injected into the striatum, indicating the modulatory influence of the basal ganglia. Further details on body shaking are provided by its reduced response to harmaline after 5-HT depletion caused by intraventricular 5,7-DHT, electrolytic lesions of the medial or dorsal raphe, and lesions of the inferior olive caused by systemic injection of 3-acetylpyridine along with those found in Agtpbp1pcd or nr cerebellar mouse mutants. Yet the influence of the climbing fiber pathway on other signs of the 5-HT syndrome remains to be determined.

The Neural Representation of Binaural Sound Localization Cues Across Different Subregions of the Chicken's Inferior Colliculus.

The sound localization behavior of the nocturnally hunting barn owl and its underlying neural computations is a textbook example of neuroethology. Differences in sound timing and level at the two ears are integrated in a series of well-characterized steps, from brainstem to inferior colliculus (IC), resulting in a topographical neural representation of auditory space. It remains an important question of brain evolution: How is this specialized case derived from a more plesiomorphic pattern? The present study is the first to match physiology and anatomical subregions in the non-owl avian IC. Single-unit responses in the chicken IC were tested for selectivity to different frequencies and to the binaural difference cues. Their anatomical origin was reconstructed with the help of electrolytic lesions and immunohistochemical identification of different subregions of the IC, based on previous characterizations in owl and chicken. In contrast to barn owl, there was no distinct differentiation of responses in the different subregions. We found neural topographies for both binaural cues but no evidence for a coherent representation of auditory space. The results are consistent with previous work in pigeon IC and chicken higher-order midbrain and suggest a plesiomorphic condition of multisensory integration in the midbrain that is dominated by lateral panoramic vision.

The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Targeting DBS to the centrolateral thalamic nucleus improves movement in a lesion-based model of acquired cerebellar dystonia in mice.

Dystonia is the third most common movement disorder and an incapacitating co-morbidity in a variety of neurologic conditions. Dystonia can be caused by genetic, degenerative, idiopathic, and acquired etiologies, which are hypothesized to converge on a "dystonia network" consisting of the basal ganglia, thalamus, cerebellum, and cerebral cortex. In acquired dystonia, focal lesions to subcortical areas in the network - the basal ganglia, thalamus, and cerebellum - lead to a dystonia that can be difficult to manage with canonical treatments, including deep brain stimulation (DBS). While studies in animal models have begun to parse the contribution of individual nodes in the dystonia network, how acquired injury to the cerebellar outflow tracts instigates dystonia; and how network modulation interacts with symptom latency remain as unexplored questions. Here, we present an electrolytic lesioning paradigm that bilaterally targets the cerebellar outflow tracts. We found that lesioning these tracts, at the junction of the superior cerebellar peduncles and the medial and intermediate cerebellar nuclei, resulted in acute, severe dystonia. We observed that dystonia is reduced with one hour of DBS of the centrolateral thalamic nucleus, a first order node in the network downstream of the cerebellar nuclei. In contrast, one hour of stimulation at a second order node in the short latency, disynaptic projection from the cerebellar nuclei, the striatum, did not modulate the dystonia in the short-term. Our study introduces a robust paradigm for inducing acute, severe dystonia, and demonstrates that targeted modulation based on network principles powerfully rescues motor behavior. These data inspire the identification of therapeutic targets for difficult to manage acquired dystonia.

Role of the median preoptic nucleus in the development of chronic deoxycorticosterone acetate (DOCA)-salt hypertension.

We have previously reported that the subfornical organ (SFO) does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the organum vasculosum of the lamina terminalis (OVLT) plays a significant role in the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Since efferent fibers of the OVLT project to and through the median preoptic nucleus (MnPO), the present study was designed to test the hypothesis that the MnPO is necessary for DOCA-salt hypertension in the rat. Male Sprague-Dawley rats underwent SHAM (MnPOsham; n = 5) or electrolytic lesion of the MnPO (MnPOx; n = 7) followed by subsequent unilateral nephrectomy and telemetry instrumentation. After recovery and during the experimental protocol, rats consumed a 0.1% NaCl diet and 0.9% NaCl drinking solution. Mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). The chronic pressor response to DOCA was attenuated in MnPOx rats by Day 11 of treatment and continued such that MAP increased 25 ± 3 mmHg in MnPOsham rats by Day 21 of DOCA compared to 14 ± 3 mmHg in MnPOx rats. These results support the hypothesis that the MnPO is an important brain site of action and necessary for the full development of DOCA-salt hypertension in the rat.

Effects of OVLT or MnPO lesion on the gut microbiome

Hypertension is a multifaceted condition affecting 700 million people worldwide, and despite decades of study, several aspects of its complex pathophysiology remain unclear. Changes in the gut microbiome have been associated with hypertension, though the cause and effect are not well defined. Historically, circumventricular organs in the brain, such as the organum vasculosum of the lamina terminalis (OVLT), and its central downstream nucleus the median preoptic nucleus (MnPO) have been shown to play a role in the pathogenesis of hypertension. Studies from our lab have demonstrated roles of both the OVLT and MnPO in the pathogenesis of angiotensin II mediated hypertension. Furthermore, we have previously reported that DOCA-salt treated OVLT lesioned rats had attenuated hypertension, and a gut microbial population more closely resembling normal controls, compared to sham lesioned rats. Lastly, we have recently shown the MnPO to be necessary in mediating DOCA-salt hypertension in the rat. Because data suggests changes in the gut microbiome occurred during the attenuated hypertensive response in lesioned animals, it is still unclear whether these changes occurred due to and shortly after the lesion, or subsequently during the hypertensive stimulus in lesioned animals. Therefore, the goal of this study was to further define the relationship between an OVLT or MnPO lesion and consequent changes in the gut microbiome without any hypertensive stimulus. Male Sprague Dawley rats underwent electrolytic lesion or sham operation using stereotaxic surgery with predetermined coordinates and settings. After 7 days, brain and regional gut tissues were harvested for analysis. Gut microbial genomic data from lesioned and sham rats were analyzed, and PCoA analysis showed statistically significant differences in microbiome composition between OVLT lesioned and sham rats in most gut regions. Generally, Shannon diversity analysis revealed sham rats had a more diverse population than OVLT lesioned rats, though both had a relatively similar spread of species abundance. Additionally, there was a common trend of higher relative abundance of Ligilactobacillus in lesioned rats for all four gut regions. In conclusion, the OVLT lesion itself has effects on the diversity of the gut microbiome, which suggest an OVLT-gut microbiome link that may contribute to attenuating hypertension. This study was supported by University of Minnesota Grant-In-Aid of Research, Artistry and Scholarship #546839 and a University of Minnesota Lillehei Heart Institute Collaborative Pilot Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A ubiquitous spectrolaminar motif of local field potential power across the primate cortex

The mammalian cerebral cortex is anatomically organized into a six-layer motif. It is currently unknown whether a corresponding laminar motif of neuronal activity patterns exists across the cortex. Here we report such a motif in the power of local field potentials (LFPs). Using laminar probes, we recorded LFPs from 14 cortical areas across the cortical hierarchy in five macaque monkeys. The laminar locations of recordings were histologically identified by electrolytic lesions. Across all areas, we found a ubiquitous spectrolaminar pattern characterized by an increasing deep-to-superficial layer gradient of high-frequency power peaking in layers 2/3 and an increasing superficial-to-deep gradient of alpha-beta power peaking in layers 5/6. Laminar recordings from additional species showed that the spectrolaminar pattern is highly preserved among primates—macaque, marmoset and human—but more dissimilar in mouse. Our results suggest the existence of a canonical layer-based and frequency-based mechanism for cortical computation.

Os benefícios do exercício físico de alta intensidade antes e após a indução da doença de Parkinson em ratos

Abstract High-intensity physical activity is a non-pharmacological intervention that has been tested as a treatment for Parkinson’s disease (PD). The objective of the study was to investigate the benefits of high-intensity physical exercise on the number of neurons and astrocytes in a a rat model of Parkinson’s disease submitted to training before and after the inducing injury. Seventy Wistar rats were used, distributed as follows: nine rats trained before PD induction (DP-Exa), nine trained after PD induction (DP-Exd), 10 trained before and after PD induction (DP-Exad), and nine sedentary rats (DP-Sed). There were also the same groups but with the rats exposed to the sham surgery (control). High-intensity physical exercise on a vertical ladder was performed before and/or after PD induction for 5 days/week, 30-45 min a day, for 4 weeks. PD was induced with an electrolytic lesion (AP -4.9, ML 1.7, and DV 8.1). At the end of the experiment, the brain was removed for Nissl staining and immunohistochemistry of glial fibrillary acidid protein (GFAP) in the substantia nigra and striatum. The DP-Exa, Sham-Exa, DP-Exad, and Sham-Exad groups showed a greater number of neurons and higher expression of GFAP in the substantia nigra and stiatum compared with the the DP-Exd, Sham-Exd, DP-Sed, and Sham-Sed groups. Thus, rats that performed high-intensity training before or before and after PD induction had higher densities of neurons and astrocytes.

Testosterone signaling pathways for reducing neuropathic pain in a rat model of spinothalamic tract lesion.

Most individuals who suffer from spinal cord injury (SCI) experience neuropathic pain, which currently has no effective treatment. In this study, we examined how testosterone affects neuropathic pain resulting from SCI. We administered three different doses of testosterone (4, 8, 16 mg/kg, intraperitoneal) to male rats after an electrolytic lesion of the spinothalamic tract. We then conducted behavioral tests, including open field and von Frey tests, within 28 days post-SCI. On day 28 after SCI, we analyzed spinal tissue using western blot to measure the levels of ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), phospho-extracellular signal-regulated kinase (p-ERK1/2), and p-P38 at the injury site. The results showed that testosterone significantly improved both motor activity and mechanical allodynia compared to the SCI-only group. Testosterone also inhibited microglia and astrocyte activation. Furthermore, testosterone significantly decreased p-P38 and p-ERK levels. The findings indicate that testosterone may alleviate SCI-induced neuropathic pain by inhibiting the activation of astrocytes and microglia, as well as suppressing MAPK signaling pathways.

Study of TMEM106B expression levels under neurodegenerative conditions

AbstractBackgroundTMEM106B is a transmembrane protein involved in dendrite morphogenesis and lysosome trafficking. TMEM106B was identified as a susceptibility gene for frontotemporal lobar degeneration with TDP‐43 inclusions (FTLD‐TDP). Brain tissue from patients with FTLD‐TDP showed increased mRNA levels of TMEM106B compared to normal controls (Van Deerlin et al, Nat Genet 2010). Our goal is to study TMEM106B expression levels in other neurodegenerative conditions such as progressive supranuclear palsy (PSP), Alzheimer’s disease (AD) and a well‐established mouse model of entorhinal cortex lesions (ECL).MethodUnilateral electrolytic lesions to the entorhinal cortex were conducted on two‐to‐three months old male C57BL/6j mice by stereotaxic surgery. For sham‐operated animals, the electrode was lowered only 1 mm without current and sacrifices were performed on the same day. All other lesioned mice were sacrificed 2, 7, 14, 21 or 40 days post‐lesion (DPL). Total RNA was extracted from frozen ipsilateral and contralateral hippocampi and expression profiles were measured with the Affymetrix Mouse ClariomTM D Assay. The Mayo Clinic Brain Bank collected RNA samples from temporal cortex and measured gene expression levels using next‐generation RNA sequencing (RNAseq). Results are available for 274 subjects with the following conditions: PSP, N = 84; AD, N = 82; pathological aging (PA), N = 30; and cognitively unimpaired (CU), N = 78.ResultIn the ECL mouse model, ipsilateral Tmem106b expression levels were significantly reduced during the deafferentation phase (DPL2: p = 0.046) and reached maximum levels during the reinnervation phase (DPL14: p = 0.030 and DPL21: p = 0.019), compared to sham‐operated animals. In human temporal cortices, TMEM106B expression increased progressively from CU (10.76±0.62), to PSP (11.25±0.43), PA (12.13±1.27) and finally AD (13.10±0.44) (mean CPM ±SEM). TMEM106B mRNA levels were significantly higher in AD compared to CU (p = 0.002) and PSP (p = 0.003).ConclusionElevated levels of TMEM106B in FTLD‐TDP, AD and during the reinnervation phase of the ECL mouse model suggest an active response to tissue damage that is consistent with compensatory synaptic and terminal remodeling, independently from tau‐mediated pathology. This hypothesis is consistent with TMEM106B levels found in PSP, which is characterized by abundant neurofibrillary tangles that differ in both distribution and composition from those associated with AD.

Mediation of mPFC-LHb pathway in acupuncture inhibition of cocaine psychomotor activity.

The medial prefrontal cortex (mPFC) and the lateral habenula (LHb) play roles in drug addiction and cognitive functions. Our previous studies have suggested that acupuncture at Shenmen (HT7) points modulates mesolimbic reward system in order to suppress drug-induced addiction behaviours. To explore whether an mPFC-LHb circuit mediates the inhibitory effects of acupuncture on addictive behaviours, we examined the projection from mPFC to LHb, excitation of mPFC neurons during acupuncture stimulation, the effects of optogenetic modulation of mPFC-LHb on HT7 inhibition of cocaine-induced locomotion and the effect of mPFC lesion on HT7 inhibition of nucleus accumbens (NAc) dopamine release. Acupuncture was applied at bilateral HT7 points for 20 s, and locomotor activity was measured in male Sprague-Dawley rats. Although cocaine injection significantly increased locomotor activity, HT7 acupuncture suppressed the cocaine-induced locomotion. The inhibitory effect of HT7 on cocaine-enhanced locomotion was blocked by optogenetic silencing of the mPFC-LHb circuit. In vivo extracellular recordings showed that HT7 acupuncture evoked an increase in the action potentials of mPFC neurons. Optopatch experiment proved glutamatergic projections from mPFC to LHb. HT7 acupuncture suppressed NAc dopamine release following cocaine injection, which was blocked by electrolytic lesion of mPFC. These results suggest the mediation of mPFC-LHb circuit in the inhibitory effects of acupuncture on cocaine psychomotor activity in rats.

The central amygdala modulates distinctive conflict-like behaviors in a naturalistic foraging task.

Conflict situations elicit a diverse range of behaviors that extend beyond the simplistic approach or avoidance dichotomy. However, many conflict-related studies have primarily focused on approach suppression, neglecting the complexity of these behaviors. In our study, we exposed rats to a semi-naturalistic foraging task, presenting them with a trade-off between a food reward and a predatory threat posed by a robotic agent. We observed that rats displayed two conflict-like behaviors (CLBs)-diagonal approach and stretched posture-when facing a robotic predator guarding a food pellet. After electrolytic lesions to the central amygdala (CeA), both conflict behaviors were significantly reduced, accompanied by a decrease in avoidance behavior (hiding) and an increase in approach behavior (frequency of interactions with the robot). A significant negative correlation between avoidance and approach behaviors emerged after the CeA lesion; however, our data suggest that CLBs are not tightly coupled with either approach or avoidance behaviors, showing no significant correlation to those behaviors. Our findings indicate that the CeA plays a crucial role in modulating conflict behaviors, competing with approach suppression in risky situations.

The anterior insular cortex processes social recognition memory

Impaired social abilities are characteristics of a variety of psychiatric disorders such as schizophrenia, autism spectrum disorder, and bipolar disorder. Studies consistently implicated the relationship between the anterior insular cortex (aIC) and social ability, however, how the aIC involves in processing specific subtypes of social ability was uninvestigated. We, therefore, investigated whether the absence or presence of the aIC affects the social behaviors of mice. We found that electrolytic lesions of the aIC specifically impaired mice’s ability to recognize a novel stranger mouse, while the sociability of the aIC-lesioned mice was intact. Interestingly, the aIC-lesioned mice were still distinguished between a mouse that had been housed together before the aIC lesion and a novel mouse, supporting that retrieval of social recognition memory may not involve the aIC. Additional behavioral tests revealed that this specific social ability impairment induced by the aIC lesion was not due to impairment in olfaction, learning and memory, locomotion, or anxiety levels. Together our data suggest that the aIC is specifically involved in processing social recognition memory, but not necessarily involved in retrieving it.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BackgroundMechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry.ResultsMechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit.ConclusionThese findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Role of the median preoptic nucleus in the development of chronic DOCA-salt hypertension

Lesions of the anteroventral third ventricle (AV3V region) are known to prevent many forms of experimental hypertension, including mineralocorticoid (DOCA-salt) hypertension in the rat. However, AV3V lesions include the organum vasculosum of the lamina terminalis (OVLT), portions of the median preoptic nucleus (MnPO), as well as efferent fibers from the subfornical organ (SFO), thereby limiting the ability to define the individual contribution of these structures to the prevention of experimental hypertension. We have previously reported that the SFO does not contribute to the chronic hypertensive response to DOCA-salt in rats, and yet the OVLT plays a significant role in the development of DOCA-salt hypertension. Since efferent fibers of the OVLT project to and through the MnPO, the present study was designed to test the hypothesis that the MnPO is necessary for DOCA-salt hypertension in the rat. Male Sprague-Dawley rats underwent unilateral nephrectomy followed by a week of recovery, and subsequent SHAM (n=5) or electrolytic lesion of the MnPO (MnPOx; n=7). Throughout another week of recovery and during the experimental protocol, rats consumed a 2% NaCl diet and 0.9% NaCl drinking solution. 24-hour mean arterial pressure (MAP) was recorded telemetrically 5 days before and 21 days after DOCA implantation (100 mg/rat; SQ). No differences in the 5-day average control MAP were observed between groups (MnPOx: 104 ± 1 mmHg; SHAM: 107±2 mmHg). The chronic pressor response to DOCA was attenuated in MnPOx rats by day 11 of treatment and continued such that MAP increased 25±3 mmHg in SHAM rats by day 21 of DOCA compared to 14±3 mmHg in MnPOx rats. These results support the hypothesis that the MnPO is an important brain site of action for the pathogenesis of DOCA-salt hypertension in the rat. University of Minnesota Grant In Aid #546839 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Impact of fornix lesions on tone-off delay vs tone-on trace eyeblink conditioning in rats

Research has shown differences in the neural mechanisms that support trace and delay eyeblink conditioning. The present experiment furthered this investigation by examining the effect of electrolytic fornix lesions on acquisition of trace and delay eyeblink conditioning in the rat. Importantly, the conditioned stimulus (CS) for trace conditioning was a standard tone-on cue, and the CS for delay conditioning was either a tone-off or tone-on CS. The results showed that fornix lesions impaired trace-, but not delay conditioning in rats trained with the tone-on CS or tone-off CS. The findings are consistent with previous studies that found trace-, but not delay eyeblink conditioning is a hippocampal dependent form of associative learning. Our results also indicate that the neural pathways for tone-off delay conditioning and tone-on trace conditioning are different, even though the structural composition of a tone-off CS and the trace conditioning interval are the same cue (i.e., the absence of sound). These findings indicate that the absence of a sensory cue (i.e., tone-off CS) and the presence of a sensory cue (i.e., tone-on CS) have equivalent associative value and effectiveness for engaging the neural pathways that support delay eyeblink conditioning.

Differential Encoding of Trace and Delay Fear Memory in the Entorhinal Cortex.

Trace fear conditioning is characterized by a stimulus-free trace interval (TI) between the conditioned stimulus (CS) and the unconditioned stimulus (US), which requires an array of brain structures to support the formation and storage of associative memory. The entorhinal cortex (EC) has been proposed to provide essential neural code for resolving temporal discontinuity in conjunction with the hippocampus. However, how the CS and TI are encoded at the neuronal level in the EC is not clear. In Exp. 1, we tested the effect of bilateral pre-training electrolytic lesions of EC on trace vs. delay fear conditioning using rats as subjects. We found that the lesions impaired the acquisition of trace but not delay fear conditioning confirming that EC is a critical brain area for trace fear memory formation. In Exp. 2, single-unit activities from EC were recorded during the pre-training baseline and post-training retention sessions following trace or delay conditioning. The recording results showed that a significant proportion of the EC neurons modulated their firing during TI after the trace conditioning, but not after the delay fear conditioning. Further analysis revealed that the majority of modulated units decreased the firing rate during the TI or the CS. Taken together, these results suggest that EC critically contributes to trace fear conditioning by modulating neuronal activity during the TI to facilitate the association between the CS and US across a temporal gap.