시험 의 일주일 변이 및 성 차이 안 해마 신경생리학 및 공간 기억 부분 1
Dec 06, 2023
추상적인
일주기 리듬 아르 생물학적 과정 그것 주기 가로질러 24 시간 및 조절 많은 면 의 신경생리학, 포함 학습 및 기억. 일주기 변이 안 공간 기억 작업 성과 is 잘 문서화된; 그러나, the 효과 의 섹스 가로지르는 일주기 시간 (CT) 잔류 불분명.
In 신경생리학, 저기 is a 구조 called synapse, which is an 적분 부분 의 the 신경 시스템. 시냅스 are the 장소 where information is transmitted between neurons, and memory is based on synapses. When a neuron receives information, it communicates with other neurons through synapses and transmits the information. the strengthening or weakening of these contacts forms the basis for memory formation and change.
기억 is 그냥 the 결과 of multiple 교환 and 계산 between different neurons in the the human brain. The number of neurons in the body is fixed, that is, our memory reserve is fixed. 그러므로, 개선 메모리 수단 개선 the strength of connections between neurons, as well as the number and quality of connections between synapses, which require further knowledge of neurophysiology.
그러므로, 신경생리학 연구 is 매우 유익한 to 개선 개인 기억. 학습 about 신경생리학 can help us better understand how the human brain works, allowing us to improve memory through exercise and training. some methods include strengthening the connections between neurons by reading more and thinking more, and improving the quantity and quality of synapses by performing various mental exercises.
In short, neurophysiological research can not only help us better understand the relationship between the human brain and memory but also provide various methods and techniques to improve individual memory. 그러므로, 우리는 should 적극적으로 learn relevant knowledge about neurophysiology to create a better environment for our memory. It can be seen that we need to improve our memory. 육종 사막 생물 할 수 있다 현저하게 개선 기억력 왜냐하면 육종 사막산 이다 a 전통적 중국어 약용 재료 포함 많은 독특한 효과, 하나 의 어떤 개선 기억. 그 효능 의 다진 고기 온다 에서 그 다양한 활성 성분 그것 함유, 포함 산, 다당류, 플라보노이드, 등. 이들 성분 할 수 있다 촉진 뇌 건강 in 다양한 방법.
추가, little is knownregarding the impact of time-of-day on hippocampal neuronal physiology. Here, we investigated the influenceof both sex and time of day on hippocampal neurophysiology and memory in mice. Performance on the objectlocation memory (OLM) task depended on both circadian time and sex, with memory enhanced at night inmales but during the day in females. 장기 시냅스 강화 (LTP) 크기 at CA3-CA1 시냅스와스 그레이터 at 밤 비교 와 낮 in 둘 다 성.
Next, we measured spontaneous synaptic excitationand inhibition onto CA1 pyramidal neurons. Frequency and amplitude of inhibition were greater during the daycompared with night, regardless of sex. Frequency and amplitude of excitation were larger in females, compared with males, independent of time-of-day, although both time-of-day and sex influenced presynaptic release probability.
At night, CA1 pyramidal neurons showed enhanced excitability (action potential firing and/orbaseline potential) that was dependent on synaptic excitation and inhibition, regardless of sex. This study emphasizes the importance of sex and time of day in hippocampal physiology, especially given that many neurologic disorders impacting the hippocampus are linked to circadian disruption and present differently in menand women. Knowledge about how sex and circadian rhythms affect hippocampal physiology can improve thetranslational relevancy of therapeutics and inform the appropriate timing of existing treatments.
키워드:
일주기 % 3B 해마 % 3B 메모리 % 3B 가소성 % 3B 리듬 % 3B 시냅스.
중요성 진술
일주기 리듬 조절 많은 양상 의 신경생리학, 포함 인지. 그러나, 더 영향 의 시간 의 일 및 섹스 에 해마 신경생리학 및 해마 의존성 기억 잔재 크게 미개척.
여기, 우리 보고서 그것 더 일주기 조절 의 대상 위치 기억 (OLM) is 성별에 따라 다릅니다. 게다가,검사 의 해마 생리학 가로질러 시간 안에 모두 남녀 공개: 강화된 장기 시냅스전동화 at 밤, 큰 낮 억제 시냅스 전달 온토 CA1 피라미드 뉴런, 효과 의 둘 다섹스 및 시간 온 흥분 시냅스 전송 온토 CA1 피라미드 뉴런, 및 강화 야간 흥분성 의 CA1 피라미드 뉴런 that is 의존 on both 시냅스 입력 및 위치 along 전방-후방 해마 축. 이들 결과 밑줄 the 중요성 의 회계 for sex, 지역 위치, and 시간 of day in the study of hippocampal 생리학.
소개
The 해마 is the seat 의 학습 and memory in 뇌 and its 기본 출력 is 생성 by the principal cells (즉, , 피라미드 뉴런) in area CA1. Action potential firing by a CA1 pyramidal neuron, like any otherneuron, is a combined function of excitatory and inhibitorysynaptic drive, intrinsic membrane properties regulatingexcitability, and neuromodulators (Spruston, 2008).
A 상대적으로 미탐사 패싯 안에서 the 해마 is how CA1피라미드 뉴런 생리학 is modulated by time of day. At the cellular level, time-of-day variations in biological function are generated by a transcriptional-translational feedback loop (Partch et al., 2014). 조직 시계 통통해 the body are 계층적으로 조직화 in a system that drives the timing of 24-hour rhythms in physiologyand behavior, enableing organisms to adapt to and anticipate 정기적으로 occurring events in their environment(Pilorz et al., 2020; Buijs et al., 2021).
일주기 조절의 생리적 과정 is 유리, 및 조절장애 의 일주기 리듬 can 촉진 및 악화 질병 발병 및 증상 (Logan and McClung,2019; Colwell, 2021). 그러므로, 이해 the circadianinfluence on 생리학 is 중요한 for designing interventions for 질병 with circadian dysfunction, such asneurodegenerative diseases (Lee et al., 2021).
더욱이,the majority of foundational knowledge concerning fundamental principles of hippocampal physiology is based onstudies conducted in nocturnal, mostly male, 설치류 during their inactive phase (daytime). 동안 the the scientificcommunity has bestarted to address the importance of sexas a factor in biomedical research, the importance of-time-of-day is still relatively underemphasized. The overarching goal of this study was to begin to unveil how sexand time of day interact to influence daily variation in hippocampal physiology and function.
The suprachiasmatic nucleus (SCN) of the 시상하부 is the principal orchestrator of the endogenous circadian network, and the electrical properties of SCN neurons vary across time of day.
일주기 조절의 신경세포 흥분성 is 광범위한 in the 포유류의 뇌 (Paul et al., 2020) and has been observed in arange of species, including 설치류 (Snider et al., 2018),Drosophila (Cao and Nitabach, 2008; Sheeba, 2008), andzebrafish (Elbaz et al., 2013). Although the SCN is theprincipal clock, autonomous circadian clocks exist in otherbrain regions, including the hippocampus (Paul et al., 2020;Hartsock and Spencer, 2020). At the 분자 level, subregions of the hippocampus 리드컬하게 express core clock proteins, with the cell body layer of area CA1 having thestrongest expression of PER2 (Jilg et al., 2010). 더욱이,over 600 genes, 포함 those 인코딩 ion channels andsynaptic proteins exhibit circadian expression in the hippocampus (Zhang et al., 2014; Renaud et al., 2015).
At the cellularlevel, long-term potentiation (LTP), a form of plasticity which specific patterns of synaptic stimulation result in along-lasting increase in the strength of synaptic transmission,is expressed at a greater magnitude at night compared withday in nocturnal mice (Chaudhury et al., 2005; Besing et al.,2017; Davis et al., 2020). Cognitive function is also regulatedby the circadian system (Wright et al. , 2012) and circadianregulation of performance on hippocampus-dependent memory assay has been demonstrated across several species(Snider et al., 2018).
However, our understanding of howsex affects circadian regulation of cognition is limited.Furthermore, evidence at the cellular level is lacking, including a detailed understanding of how time-of-day andsex regulate synaptic drive onto and membrane propertiesof CA1 pyramidal cells. Here, we sought to determine howsex and time of day modulate the hippocampal circuit:from the behavioral level down to individual neuronal physiology.
우리는 찾았다 그것 일주기 조절 의 해마-의존적 기억 이다 의존적 에 섹스, 동안 낮-밤의 차이 안에 해마 LTP 있다 아니다. 우리 또한 발견된것 시냅스 전달 및 뉴런 흥분성 변화하는 아사 기능 의 the 시간 의 일 및 밝혀진 그것 일부 의이들 변화 의존 에 섹스.
재료 및 방법
마리
모든 동물 절차 팔로우 더 가이드 for the 케어 및사용 의 실험실 동물, 미국 주 공공 보건 서비스, 및 were 승인 by the University of Alabama atBirmingham Institutional Animal Care and Use Committee. Allexperiments used 6- to 12-week-old C57BL/6J mice of bothsexes obtained from Jackson Laboratories (http://jaxmice.jax.org/strain/013636.html) or the C57BL/6J colony at the University 의 앨라배마 at 버밍엄.
생쥐 were maintainedon a 12/12 h light/dark cycle with ad libitum access to food(LabDiet 설치류 5001 by Purina) and water. 생쥐 were grouphoused in same-sex cages of four mice for behavior experiments. For all other experiments, mice were group housed insame-sex cages of two to seven mice per cage.
객체 위치 메모리 (OLM)
The object location memory (OLM) task (Snider et al.,2016) was conducted under,10 lux dim red light. Four cohorts of mice were used, with each cohort consisting ofeight males and eight females. within each cohort, micewere assigned to undergo habituation, training, and testing either during the day or during the night. In cohorts 1and 3, males were tested during the day, and femaleswere tested at night. In 코호트 2 and 4, 여성 검사 중 낮 및 남성 검사 검사 at night.
생쥐 were entrained to a 12/12 h light/dark (LD) cycle,and then habituated to the arena for 2 d at eitherZeitgeber time (ZT) four or ZT 16 (where ZT 12 refers tolights off), for day and night, 각각 (일 1–2; Fig.1A, B). 애프터 일 2, 생쥐 were 방출 into 상수 어둠 (DD) and again habituated to the arena at projectedcircadian time (CT) 4 or 16 ( 일 3–4, 어디서 CT 12 참조 the 투사 시간 의 조명 꺼짐 from the prior LD cycle;Fig. 1A, B). Mice were 허용 to acclimate to the behaviorroom for 20 min each day immediately before habituationor training/test.
습관화 일관성 의 5 최소 의 처리따라 5 최소 의 아레나 탐사 with visual cuespresent. 시각 단서 구성된 의 수직 줄무늬 on onewall and a large red X on another wall. the arenas were35.5 25.4 cm with 20.3 cm-high walls. OLM trainingand testing occurred in DD, 24 h after the final day of habituation at projected CT four or CT 16. Objects weremade with PRETEX Building Blocks (항목 No. 8030-100)and had three possible positions within the arena, all atleast 8.9 cm away from the walls.
During training, each mouse was allowed to explore anarena with two objects for 5 min. After, the mousewas return to its home cage for 30 min, during whichone of the objects from the original exploration wasmoved to a new position (the novel location) while oneremained in its original position (the familiar location;Fig. 1C). A 30-min recall period was chosen based on before published methods (Snider et al. , 2016) 및 회피 메모리 간섭 왜냐하면 의 절전 박탈또는 메모리 향상 에서 AN 밤새통 수면 기간.
In the test phase, each mouse was placed back in thearena with the novel and familiar location objects and allowed to explore for 5 min. All habituation, training, andtesting were recorded at 30 FPS (ELP Camera Model:ELP-USBFHD05MT-KL36IR). Exploration was trackedusing a computer model made via DeepLabCut. Object interaction was then analyzed using custom MATLAB(MathWorks) scripts developed by Mary Phillips (https://github.com/PhillipsML/DLC-NovelObject#dlc-novel object).For data analysis, several exclusion criteria were applied:mice that exhibited a clear side preference, mice that spentmost of their time exploring objects to try to escape the arena, and mice with a high preference for oneobject over the other during training were excluded. The discrimination index was calculated as: (time spent exploring novel object location time spent exploring familiar object location)/(time spent exploring novel object location 1time spent exploring familiar object location).
전기생리학
슬라이스 준비
생쥐 were killed with 자궁경부 탈구 and rapid decapitation at ZT {{0}}–1 or ZT 11–12 for day and night experiments, 각각. Both sex and time of day wereinterleaved. For extracellular field experiments, brainswere removed and 350-}mm coronal slices were preparedusing a VT1200 S vibratome (Leica Biosystems) in an ice-cold solution containing the following (in mM): 85 NaCl % 2c 2.5KCl % 2c 4 MgSO4 * 7H2O % 2c 0..5 CaCl2 * 2H2O, 1.25 NaH2PO4, 75자당, 25 NaHCO3, 25 포도당 포화 in 95% O2 and 5% CO2. 슬라이스 were 허용 to rest for at 최소 1 h in a 복구 솔루션 의 표준 인공 CSF (ACSF) containingthe following (in mM): 119 NaCl, 2.5 KCl, 1.3 MgSO4 * 7H2O,2.5 CaCl2 * 2H2O, 1 NaH2PO4, 26 NaHCO3, 및 11 포도당,bubbled with 95% O2/5% CO2.
For whole-cell patch-clampexperiments, brains were removed and 300-mm thick coronal slices were prepared using a VT1200 S vibratome (LeicaBiosystems) in an ice-cold solution containing the following(in mM): 110 choline chloride, 25 glucose, 7 MgCl2, 2.5 KCl,1.25 Na2PO4, 0.5 CaCl2, 1.3 Na-ascorbate, 3 Na-pyruvate,and 25 NaHCO3, bubbled with 95% O2/5% CO2.
Sliceswere 허용 to 휴식 for at 최소 1 h at 방 온도 in arecovery solution containing the following (in mM): 125 NaCl,2.5 KCl, 1.25 Na2PO4, 2 CaCl2, 1 MgCl2, 25 NaHCO3, and25 glucose, bubbled with 95% O2/5% CO2. For experiments measuring inhibitory synaptic events, 2 mM kynurenicacid was added to the recovery solution.
필드 녹화
데이터 다음 획득 에서 ZT 1–6 또는 ZT 12–18 for 낮 밤 녹음, 각각. 관상 해마 조각인간 배치 in a 침수 챔버 및 연속적관류 with 표준 ACSF at 3–5 ml/min and 26–28 degree . Schaffer collateral 축삭 were 자극 using a 양극자극 전극 배치 in the 지층 radiatum of areaCA3. 필드 EPSPs (fEPSP) were with with a recordingelectrode placed in the stratum radiatum of area CA1, within200–300mm of the stimulating electrode.
초기 기울기 의 fEPSPs (fEPSP 기울기) was 측정 at the linear regionimmediately following the fiber volley and preceding thefEPSP peak. Data were acquired and analyzed usingpCLAMP10/11(Molecular Devices). Data were recordedusing a Kerr Scientific S2 amplifier (Kerr Tissue RecordingSystem, Kerr Scientific Instruments). Signals were digitized at 10 kHz (Digidata 1550B).
입력-출력 (I/O) 곡선 were 생성 by 측정 the 기울기 of fEPSPs from CA1 stratum radiatum inresponse to a series of 증가 자극 intensities(0.2–200 mA, D 10 mA) at the Schaffer Collaterals.Baseline fEPSPs were obtained by delivering a 0.1-Hzstimulation to elicit fEPSPs of approximately 0.20 mV/msfor 20 min.
장기 강화 (LTP) 실험 있었다 실시 얻고 및 유지 a 안정 기준선fEPSP 응답 for 20 min, and then LTP was 유도 bydelivering a 고주파 자극 (HFS; 100 Hz;0.5 sduration; delivered 2 with 15-s interval). This weakerstimulation protocol was chosen to 회피 마스킹 aday/night difference in LTP magnitude (Besing et al.,2017; Davis et al., 2020). 이후 HFS% 2c fEPSP 슬로프 녹화 40 분.
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